11-61826344-C-T

Variant names:

• chr11-61826344-C-T
• rs174568
• ENST00000257261.10:c.141+9918C>T

Variant summary

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

The NM_001281501.1(FADS2):​c.141+9918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 702,380 control chromosomes in the GnomAD database, including 43,527 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 0.29 (8107 hom., cov: 32)
  • Exomes 𝑓: 0.34 (35420 hom.)
• Consequence: FADS2 NM_001281501.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 76 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281501.1. 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_001281501.1		c.141+9918C>T		intron	N/A	NP_001268430.1	O95864-2
	FADS2	NM_001281502.1		c.114+9648C>T		intron	N/A	NP_001268431.1	O95864-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS2	ENST00000257261.10	TSL:1	c.141+9918C>T		intron	N/A	ENSP00000257261.6	O95864-2
	FADS2	ENST00000517839.1	TSL:3	c.*105C>T		3_prime_UTR	Exon 3 of 3	ENSP00000429693.1	E5RHL3
	FADS2	ENST00000522056.5	TSL:2	c.114+9648C>T		intron	N/A	ENSP00000429500.1	O95864-4

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43548 AN: 152004 Hom.: 8085 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.334

GnomAD2 exomes AF: 0.372 AC: 47785 AN: 128284 AF XY: 0.350

Gnomad AFR exome AF: 0.0698

Gnomad AMR exome AF: 0.650

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.572

Gnomad FIN exome AF: 0.416

Gnomad NFE exome AF: 0.333

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.337 AC: 185357 AN: 550256 Hom.: 35420 Cov.: 0 AF XY: 0.325 AC XY: 96680 AN XY: 297876

African (AFR) AF: 0.0777 AC: 1229 AN: 15808

American (AMR) AF: 0.632 AC: 21952 AN: 34712

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 5594 AN: 20026

East Asian (EAS) AF: 0.444 AC: 14263 AN: 32104

South Asian (SAS) AF: 0.173 AC: 10841 AN: 62776

European-Finnish (FIN) AF: 0.422 AC: 14003 AN: 33188

Middle Eastern (MID) AF: 0.259 AC: 1054 AN: 4076

European-Non Finnish (NFE) AF: 0.333 AC: 105627 AN: 316964

Other (OTH) AF: 0.353 AC: 10794 AN: 30602

GnomAD4 genome AF: 0.286 AC: 43582 AN: 152124 Hom.: 8107 Cov.: 32 AF XY: 0.293 AC XY: 21750 AN XY: 74348

African (AFR) AF: 0.0785 AC: 3259 AN: 41538

American (AMR) AF: 0.487 AC: 7446 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 987 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2873 AN: 5174

South Asian (SAS) AF: 0.179 AC: 862 AN: 4820

European-Finnish (FIN) AF: 0.419 AC: 4426 AN: 10560

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22702 AN: 67970

Other (OTH) AF: 0.338 AC: 712 AN: 2108

Alfa AF: 0.277 Hom.: 4774

Bravo AF: 0.288

Asia WGS AF: 0.371 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.45
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs174568; hg19: chr11-61593816; COSMIC: COSV53898928; COSMIC: COSV53898928;