rs174546

Variant names:

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BA1BP4_Strong

The NM_013402.7(FADS1):c.*53G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.333 (AC=495,736) in the gnomAD database across 1,490,570 control chromosomes, including 90,175 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.626. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 8149 hom., cov: 32)

Exomes 𝑓: 0.34 ( 82026 hom. )

Consequence

FADS1
NM_013402.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.419

Publications

381 publications found

Variant links:

Genes affected

FADS1 (HGNC:3574): (fatty acid desaturase 1) The protein encoded by this gene is a member of the fatty acid desaturase (FADS) gene family. Desaturase enzymes regulate unsaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both of which are characterized by conserved histidine motifs. This gene is clustered with family members FADS1 and FADS2 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. [provided by RefSeq, Jul 2008]

FADS1 links:

FADS2 (HGNC:3575): (fatty acid desaturase 2) The protein encoded by this gene is a member of the fatty acid desaturase (FADS) gene family. Desaturase enzymes regulate unsaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both of which are characterized by conserved histidine motifs. This gene is clustered with family members at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

FADS2 links:

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new If you want to explore the variant's impact on the transcript NM_013402.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6256 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013402.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	NM_013402.7	MANE Select	c.*53G>A		3_prime_UTR	Exon 12 of 12	NP_037534.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FADS1	ENST00000350997.12	TSL:1 MANE Select	c.*53G>A	3_prime_UTR	Exon 12 of 12	ENSP00000322229.9	A0A0A0MR51
FADS1	ENST00000935427.1		c.*53G>A	3_prime_UTR	Exon 12 of 12	ENSP00000605486.1
FADS1	ENST00000935426.1		c.*53G>A	3_prime_UTR	Exon 11 of 11	ENSP00000605485.1

Frequencies

GnomAD3 genomes

AF:

0.287

AC:

43680

AN:

152002

Hom.:

8127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0780

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.336

GnomAD4 exome

AF:

0.338

AC:

452022

AN:

1338450

Hom.:

82026

Cov.:

AF XY:

0.332

AC XY:

220719

AN XY:

664056

show subpopulations

African (AFR)

AF:

0.0603

AC:

1841

AN:

30528

American (AMR)

AF:

0.633

AC:

22707

AN:

35900

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

6915

AN:

24782

East Asian (EAS)

AF:

0.456

AC:

16348

AN:

35878

South Asian (SAS)

AF:

0.171

AC:

13356

AN:

78002

European-Finnish (FIN)

AF:

0.424

AC:

20856

AN:

49190

Middle Eastern (MID)

AF:

0.256

AC:

1425

AN:

5570

European-Non Finnish (NFE)

AF:

0.341

AC:

349122

AN:

1022540

Other (OTH)

AF:

0.347

AC:

19452

AN:

56060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

14651

29301

43952

58602

73253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11124

22248

33372

44496

55620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.287

AC:

43714

AN:

152120

Hom.:

8149

Cov.:

AF XY:

0.293

AC XY:

21808

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0778

AC:

3230

AN:

41532

American (AMR)

AF:

0.488

AC:

7454

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

994

AN:

3470

East Asian (EAS)

AF:

0.554

AC:

2856

AN:

5156

South Asian (SAS)

AF:

0.179

AC:

864

AN:

4824

European-Finnish (FIN)

AF:

0.421

AC:

4445

AN:

10564

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.336

AC:

22840

AN:

67972

Other (OTH)

AF:

0.340

AC:

717

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1443

2885

4328

5770

7213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.322

Hom.:

38223

Bravo

AF:

0.288

Asia WGS

AF:

0.375

AC:

1302

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.383

AC:

46941

AN:

122658

ABraOM SABE-WGS-1171

AF:

0.300

AC:

702

AN:

2342

Hom.:

101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.3

(source)

DANN

Benign

0.78

PhyloP100

0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over