chr11-61803311-T-C

Variant names:

• chr11-61803311-T-C
• rs174547
• NM_013402.7:c.1248+52A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013402.7(FADS1):​c.1248+52A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,472,252 control chromosomes in the GnomAD database, including 90,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.29 (8147 hom., cov: 32)
  • Exomes 𝑓: 0.34 (82457 hom.)
• Consequence: FADS1 NM_013402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366
• Publications: 394 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

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.1248+52A>G		intron	N/A	NP_037534.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS1	ENST00000350997.12	TSL:1 MANE Select	c.1248+52A>G		intron	N/A	ENSP00000322229.9	A0A0A0MR51
	FADS1	ENST00000935427.1		c.1248+52A>G		intron	N/A	ENSP00000605486.1
	FADS1	ENST00000935426.1		c.1248+52A>G		intron	N/A	ENSP00000605485.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43701 AN: 151986 Hom.: 8125 Cov.: 32

Gnomad AFR AF: 0.0782

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: 446677 AN: 1320148 Hom.: 82457 Cov.: 20 AF XY: 0.332 AC XY: 220249 AN XY: 664042

African (AFR) AF: 0.0617 AC: 1901 AN: 30788

American (AMR) AF: 0.650 AC: 28939 AN: 44492

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 7059 AN: 25304

East Asian (EAS) AF: 0.457 AC: 17794 AN: 38934

South Asian (SAS) AF: 0.170 AC: 14196 AN: 83502

European-Finnish (FIN) AF: 0.424 AC: 22571 AN: 53260

Middle Eastern (MID) AF: 0.259 AC: 1431 AN: 5518

European-Non Finnish (NFE) AF: 0.339 AC: 333548 AN: 982612

Other (OTH) AF: 0.345 AC: 19238 AN: 55738

GnomAD4 genome AF: 0.288 AC: 43735 AN: 152104 Hom.: 8147 Cov.: 32 AF XY: 0.293 AC XY: 21819 AN XY: 74354

African (AFR) AF: 0.0780 AC: 3239 AN: 41510

American (AMR) AF: 0.488 AC: 7452 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2866 AN: 5170

South Asian (SAS) AF: 0.180 AC: 867 AN: 4828

European-Finnish (FIN) AF: 0.421 AC: 4438 AN: 10550

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22849 AN: 67976

Other (OTH) AF: 0.339 AC: 717 AN: 2112

Alfa AF: 0.324 Hom.: 35025

Bravo AF: 0.288

Asia WGS AF: 0.375 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.61
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs174547; hg19: chr11-61570783; COSMIC: COSV63520556; COSMIC: COSV63520556;