rs640081

chr12-49896771-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012306.4(FAIM2):c.434+260C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,070 control chromosomes in the GnomAD database, including 30,377 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 0.62 (30377 hom., cov: 33)
• Consequence: FAIM2 NM_012306.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

Genes affected

FAIM2 (HGNC:17067): (Fas apoptotic inhibitory molecule 2) Involved in regulation of neuron apoptotic process. Acts upstream of or within negative regulation of extrinsic apoptotic signaling pathway via death domain receptors. Located in membrane raft. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAIM2	NM_012306.4	c.434+260C>T		intron_variant		ENST00000320634.8
FAIM2	XM_005268730.4	c.308+260C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAIM2	ENST00000320634.8	c.434+260C>T		intron_variant		1	NM_012306.4	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94830 AN: 151952 Hom.: 30375 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.624 AC: 94867 AN: 152070 Hom.: 30377 Cov.: 33 AF XY: 0.628 AC XY: 46711 AN XY: 74362

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.628

Alfa AF: 0.679 Hom.: 31455

Bravo AF: 0.618

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.8
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs640081; hg19: chr12-50290554;