NM_004265.4:c.*21C>T

Variant names:

• chr11-61865710-C-T
• rs482548
• NM_004265.4:c.*21C>T

Variant summary

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

The NM_004265.4(FADS2):​c.*21C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 1,602,036 control chromosomes in the GnomAD database, including 5,853 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.062 (429 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5424 hom.)
• Consequence: FADS2 NM_004265.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 33 publications found

Genes affected

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004265.4. 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
	FADS2	NM_004265.4	MANE Select	c.*21C>T		3_prime_UTR	Exon 12 of 12	NP_004256.1	O95864-1
	FADS2	NM_001281501.1		c.*21C>T		3_prime_UTR	Exon 12 of 12	NP_001268430.1	O95864-2
	FADS2	NM_001281502.1		c.*21C>T		3_prime_UTR	Exon 12 of 12	NP_001268431.1	O95864-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS2	ENST00000278840.9	TSL:1 MANE Select	c.*21C>T		3_prime_UTR	Exon 12 of 12	ENSP00000278840.4	O95864-1
	FADS2	ENST00000257261.10	TSL:1	c.*21C>T		3_prime_UTR	Exon 12 of 12	ENSP00000257261.6	O95864-2
	FADS2	ENST00000925575.1		c.*21C>T		3_prime_UTR	Exon 13 of 13	ENSP00000595634.1

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9437 AN: 152130 Hom.: 427 Cov.: 32

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0619

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.0724

GnomAD2 exomes AF: 0.0636 AC: 14936 AN: 234796 AF XY: 0.0653

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.0450

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.00124

Gnomad FIN exome AF: 0.0591

Gnomad NFE exome AF: 0.0892

Gnomad OTH exome AF: 0.0807

GnomAD4 exome AF: 0.0813 AC: 117849 AN: 1449788 Hom.: 5424 Cov.: 30 AF XY: 0.0807 AC XY: 58111 AN XY: 720348

African (AFR) AF: 0.0133 AC: 443 AN: 33290

American (AMR) AF: 0.0468 AC: 2059 AN: 43988

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3392 AN: 25884

East Asian (EAS) AF: 0.000761 AC: 30 AN: 39406

South Asian (SAS) AF: 0.0343 AC: 2920 AN: 85008

European-Finnish (FIN) AF: 0.0579 AC: 3039 AN: 52494

Middle Eastern (MID) AF: 0.107 AC: 615 AN: 5750

European-Non Finnish (NFE) AF: 0.0910 AC: 100440 AN: 1104032

Other (OTH) AF: 0.0819 AC: 4911 AN: 59936

GnomAD4 genome AF: 0.0620 AC: 9441 AN: 152248 Hom.: 429 Cov.: 32 AF XY: 0.0586 AC XY: 4366 AN XY: 74450

African (AFR) AF: 0.0176 AC: 733 AN: 41562

American (AMR) AF: 0.0565 AC: 864 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5180

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4824

European-Finnish (FIN) AF: 0.0619 AC: 657 AN: 10612

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0930 AC: 6324 AN: 67996

Other (OTH) AF: 0.0716 AC: 151 AN: 2108

Alfa AF: 0.0869 Hom.: 1167

Bravo AF: 0.0613

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.50
PhyloP100		0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs482548; hg19: chr11-61633182;