rs2072114

Variant names:

• chr11-61837743-A-G
• rs2072114
• NM_004265.4:c.208-35A>G

Variant summary

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

The NM_004265.4(FADS2):​c.208-35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,443,444 control chromosomes in the GnomAD database, including 18,227 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 0.16 (2422 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15805 hom.)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 62 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004265.4. 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_004265.4	MANE Select	c.208-35A>G		intron	N/A	NP_004256.1	O95864-1
	FADS2	NM_001281501.1		c.142-35A>G		intron	N/A	NP_001268430.1	O95864-2
	FADS2	NM_001281502.1		c.115-35A>G		intron	N/A	NP_001268431.1	O95864-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FADS2	ENST00000278840.9	TSL:1 MANE Select	c.208-35A>G		intron	N/A	ENSP00000278840.4	O95864-1
	FADS2	ENST00000257261.10	TSL:1	c.142-35A>G		intron	N/A	ENSP00000257261.6	O95864-2
	FADS2	ENST00000521849.5	TSL:1	c.208-35A>G		intron	N/A	ENSP00000431091.1	O95864-3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24292 AN: 152118 Hom.: 2411 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.0757

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.166

GnomAD2 exomes AF: 0.185 AC: 35826 AN: 193362 AF XY: 0.173

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.323

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.428

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.142 AC: 182936 AN: 1291208 Hom.: 15805 Cov.: 18 AF XY: 0.139 AC XY: 89512 AN XY: 646162

African (AFR) AF: 0.127 AC: 3790 AN: 29726

American (AMR) AF: 0.312 AC: 12154 AN: 38976

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 2993 AN: 24582

East Asian (EAS) AF: 0.345 AC: 12652 AN: 36620

South Asian (SAS) AF: 0.0685 AC: 5388 AN: 78652

European-Finnish (FIN) AF: 0.285 AC: 14498 AN: 50958

Middle Eastern (MID) AF: 0.107 AC: 591 AN: 5508

European-Non Finnish (NFE) AF: 0.125 AC: 121869 AN: 971600

Other (OTH) AF: 0.165 AC: 9001 AN: 54586

GnomAD4 genome AF: 0.160 AC: 24347 AN: 152236 Hom.: 2422 Cov.: 32 AF XY: 0.168 AC XY: 12494 AN XY: 74424

African (AFR) AF: 0.131 AC: 5424 AN: 41542

American (AMR) AF: 0.239 AC: 3650 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3472

East Asian (EAS) AF: 0.411 AC: 2129 AN: 5176

South Asian (SAS) AF: 0.0764 AC: 369 AN: 4832

European-Finnish (FIN) AF: 0.286 AC: 3029 AN: 10604

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.131 AC: 8898 AN: 68008

Other (OTH) AF: 0.169 AC: 357 AN: 2110

Alfa AF: 0.141 Hom.: 4109

Bravo AF: 0.160

Asia WGS AF: 0.236 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.30
PhyloP100		-0.47
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: rs2072114; hg19: chr11-61605215; COSMIC: COSV53898937; COSMIC: COSV53898937;