rs99780

Variant names:

• chr11-61829161-C-T
• rs99780
• NM_004265.4:c.207+564C>T

Variant summary

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

The NM_004265.4(FADS2):​c.207+564C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 153,086 control chromosomes in the GnomAD database, including 11,800 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 0.38 (11753 hom., cov: 32)
  • Exomes 𝑓: 0.27 (47 hom.)
• Consequence: FADS2 NM_004265.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 69 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FADS2	NM_004265.4	c.207+564C>T		intron_variant	Intron 1 of 11	ENST00000278840.9	NP_004256.1
FADS2	NM_001281501.1	c.142-8617C>T		intron_variant	Intron 1 of 11		NP_001268430.1
FADS2	NM_001281502.1	c.115-8617C>T		intron_variant	Intron 1 of 11		NP_001268431.1
FADS2	XM_047427889.1	c.207+564C>T		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.207+564C>T		intron_variant	Intron 1 of 11	1	NM_004265.4	ENSP00000278840.4

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58036 AN: 151970 Hom.: 11711 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.274 AC: 273 AN: 998 Hom.: 47 Cov.: 0 AF XY: 0.264 AC XY: 139 AN XY: 526

African (AFR) AF: 0.375 AC: 6 AN: 16

American (AMR) AF: 0.400 AC: 12 AN: 30

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3 AN: 22

East Asian (EAS) AF: 0.417 AC: 25 AN: 60

South Asian (SAS) AF: 0.0926 AC: 5 AN: 54

European-Finnish (FIN) AF: 0.396 AC: 19 AN: 48

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.266 AC: 186 AN: 698

Other (OTH) AF: 0.242 AC: 16 AN: 66

GnomAD4 genome AF: 0.382 AC: 58128 AN: 152088 Hom.: 11753 Cov.: 32 AF XY: 0.385 AC XY: 28613 AN XY: 74344

African (AFR) AF: 0.392 AC: 16276 AN: 41480

American (AMR) AF: 0.534 AC: 8168 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1050 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2855 AN: 5152

South Asian (SAS) AF: 0.183 AC: 882 AN: 4828

European-Finnish (FIN) AF: 0.421 AC: 4462 AN: 10590

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23228 AN: 67960

Other (OTH) AF: 0.405 AC: 854 AN: 2110

Alfa AF: 0.380 Hom.: 2509

Bravo AF: 0.396

Asia WGS AF: 0.398 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.89
PhyloP100		-1.2
PromoterAI		0.0065	Neutral
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: rs99780; hg19: chr11-61596633;