rs174575

Variant names:

• chr11-61834531-C-G
• rs174575
• NM_004265.4:c.208-3247C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 135 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 -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 VariationId 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 rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.208-3247C>G		intron_variant	Intron 1 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.142-3247C>G		intron_variant	Intron 1 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.115-3247C>G		intron_variant	Intron 1 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.208-3247C>G		intron_variant	Intron 2 of 12		XP_047283845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FADS2	ENST00000278840.9	c.208-3247C>G		intron_variant	Intron 1 of 11	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

African (AFR) AF: 0.223 AC: 9269 AN: 41484

American (AMR) AF: 0.314 AC: 4803 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3472

East Asian (EAS) AF: 0.151 AC: 778 AN: 5160

South Asian (SAS) AF: 0.125 AC: 604 AN: 4824

European-Finnish (FIN) AF: 0.223 AC: 2359 AN: 10598

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17535 AN: 67970

Other (OTH) AF: 0.267 AC: 563 AN: 2110

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

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.18
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: rs174575; hg19: chr11-61602003;