chr12-49892272-G-A

Position:

• chr12-49892272-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.435-1158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,754 control chromosomes in the GnomAD database, including 3,845 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 0.18 (3845 hom., cov: 31)
• Consequence: FAIM2 NM_012306.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAIM2	NM_012306.4	c.435-1158C>T		intron_variant		ENST00000320634.8	NP_036438.2
FAIM2	XM_005268730.4	c.309-1158C>T		intron_variant			XP_005268787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAIM2	ENST00000320634.8	c.435-1158C>T		intron_variant		1	NM_012306.4	ENSP00000321951	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26747 AN: 151636 Hom.: 3841 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.176 AC: 26769 AN: 151754 Hom.: 3845 Cov.: 31 AF XY: 0.184 AC XY: 13628 AN XY: 74140

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.0614

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.0789

Gnomad4 NFE AF: 0.0581

Gnomad4 OTH AF: 0.161

Alfa AF: 0.0808 Hom.: 1836

Bravo AF: 0.200

Asia WGS AF: 0.362 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs905619; hg19: chr12-50286055;