chr11-61834531-C-G

Position:

• chr11-61834531-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004265.4(FADS2):​c.208-3247C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,114 control chromosomes in the GnomAD database, including 4,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (4702 hom., cov: 32)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.181

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-61834531-C-G is Benign according to our data. Variant chr11-61834531-C-G is described in ClinVar as [Benign]. Clinvar id is 1269746.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADS2	NM_004265.4	c.208-3247C>G		intron_variant		ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.142-3247C>G		intron_variant			NP_001268430.1
FADS2	NM_001281502.1	c.115-3247C>G		intron_variant			NP_001268431.1
FADS2	XM_047427889.1	c.208-3247C>G		intron_variant			XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.208-3247C>G		intron_variant		1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.243 AC: 37010 AN: 151996 Hom.: 4702 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.243 AC: 37031 AN: 152114 Hom.: 4702 Cov.: 32 AF XY: 0.240 AC XY: 17846 AN XY: 74348

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.267

Alfa AF: 0.244 Hom.: 611

Bravo AF: 0.250

Asia WGS AF: 0.177 AC: 614 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2021

This variant is associated with the following publications: (PMID: 32127356) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs174575; hg19: chr11-61602003;