11-61857233-T-C

Variant names:

• chr11-61857233-T-C
• rs498793
• NM_004265.4:c.805+162T>C

Variant summary

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

The NM_004265.4(FADS2):​c.805+162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,926 control chromosomes in the GnomAD database, including 30,134 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 0.63 (30134 hom., cov: 31)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 56 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.805+162T>C		intron_variant	Intron 6 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.739+162T>C		intron_variant	Intron 6 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.712+162T>C		intron_variant	Intron 6 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.805+162T>C		intron_variant	Intron 7 of 12		XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.805+162T>C		intron_variant	Intron 6 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95242 AN: 151808 Hom.: 30111 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.620

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.627 AC: 95319 AN: 151926 Hom.: 30134 Cov.: 31 AF XY: 0.630 AC XY: 46758 AN XY: 74274

African (AFR) AF: 0.649 AC: 26898 AN: 41434

American (AMR) AF: 0.602 AC: 9191 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1997 AN: 3472

East Asian (EAS) AF: 0.907 AC: 4657 AN: 5136

South Asian (SAS) AF: 0.697 AC: 3363 AN: 4826

European-Finnish (FIN) AF: 0.608 AC: 6424 AN: 10572

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40805 AN: 67900

Other (OTH) AF: 0.622 AC: 1309 AN: 2106

Alfa AF: 0.603 Hom.: 45787

Bravo AF: 0.627

Asia WGS AF: 0.765 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.026
DANN	Benign	0.63
PhyloP100		-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: rs498793; hg19: chr11-61624705;