12-49896240-T-C

Variant names:

• chr12-49896240-T-C
• rs956864
• NM_012306.4:c.434+791A>G

Variant summary

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

The NM_012306.4(FAIM2):​c.434+791A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,020 control chromosomes in the GnomAD database, including 11,822 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 (11822 hom., cov: 32)
• Consequence: FAIM2 NM_012306.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAIM2	NM_012306.4	c.434+791A>G		intron_variant	Intron 5 of 11	ENST00000320634.8	NP_036438.2
FAIM2	XM_005268730.4	c.308+791A>G		intron_variant	Intron 4 of 10		XP_005268787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAIM2	ENST00000320634.8	c.434+791A>G		intron_variant	Intron 5 of 11	1	NM_012306.4	ENSP00000321951.3

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57329 AN: 151902 Hom.: 11799 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.378 AC: 57405 AN: 152020 Hom.: 11822 Cov.: 32 AF XY: 0.377 AC XY: 28044 AN XY: 74296

African (AFR) AF: 0.524 AC: 21708 AN: 41428

American (AMR) AF: 0.412 AC: 6296 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2269 AN: 5158

South Asian (SAS) AF: 0.419 AC: 2022 AN: 4824

European-Finnish (FIN) AF: 0.275 AC: 2902 AN: 10564

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20310 AN: 67970

Other (OTH) AF: 0.356 AC: 753 AN: 2116

Alfa AF: 0.320 Hom.: 13882

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.79
PhyloP100		-0.14
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: rs956864; hg19: chr12-50290023;