11-61828092-C-T

Variant names:

• chr11-61828092-C-T
• rs968567
• ENST00000257261.10:c.142-9686C>T

Variant summary

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

The ENST00000257261.10(FADS2):​c.142-9686C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,281,338 control chromosomes in the GnomAD database, including 18,233 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 0.11 (1214 hom., cov: 32)
  • Exomes 𝑓: 0.17 (17019 hom.)
• Consequence: FADS2 ENST00000257261.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 161 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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	XM_047427889.1	c.-299C>T		5_prime_UTR_variant	Exon 2 of 13		XP_047283845.1
FADS2	NM_001281501.1	c.142-9686C>T		intron_variant	Intron 1 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.115-9686C>T		intron_variant	Intron 1 of 11		NP_001268431.1
FADS2	NM_004265.4	c.-299C>T		upstream_gene_variant		ENST00000278840.9	NP_004256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.-299C>T		upstream_gene_variant		1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16315 AN: 151724 Hom.: 1215 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.166 AC: 187416 AN: 1129496 Hom.: 17019 Cov.: 30 AF XY: 0.164 AC XY: 88582 AN XY: 540058

African (AFR) AF: 0.0248 AC: 588 AN: 23714

American (AMR) AF: 0.0744 AC: 802 AN: 10782

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 1566 AN: 14702

East Asian (EAS) AF: 0.000576 AC: 13 AN: 22574

South Asian (SAS) AF: 0.0640 AC: 3042 AN: 47502

European-Finnish (FIN) AF: 0.0992 AC: 2048 AN: 20654

Middle Eastern (MID) AF: 0.129 AC: 389 AN: 3008

European-Non Finnish (NFE) AF: 0.183 AC: 172426 AN: 941404

Other (OTH) AF: 0.145 AC: 6542 AN: 45156

GnomAD4 genome AF: 0.107 AC: 16310 AN: 151842 Hom.: 1214 Cov.: 32 AF XY: 0.101 AC XY: 7530 AN XY: 74202

African (AFR) AF: 0.0326 AC: 1352 AN: 41452

American (AMR) AF: 0.0835 AC: 1276 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3462

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5150

South Asian (SAS) AF: 0.0560 AC: 269 AN: 4800

European-Finnish (FIN) AF: 0.100 AC: 1053 AN: 10532

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11478 AN: 67860

Other (OTH) AF: 0.130 AC: 274 AN: 2108

Alfa AF: 0.141 Hom.: 3709

Bravo AF: 0.104

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.95
PhyloP100		0.34
PromoterAI		0.81	Over-expression
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: rs968567; hg19: chr11-61595564;