chr12-49896771-G-A

Variant names:

• chr12-49896771-G-A
• rs640081
• NM_012306.4:c.434+260C>T

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+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
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012306.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAIM2	NM_012306.4	MANE Select	c.434+260C>T		intron	N/A	NP_036438.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAIM2	ENST00000320634.8	TSL:1 MANE Select	c.434+260C>T		intron	N/A	ENSP00000321951.3
	FAIM2	ENST00000550890.5	TSL:2	c.296+260C>T		intron	N/A	ENSP00000450132.1
	FAIM2	ENST00000552669.5	TSL:3	c.308+260C>T		intron	N/A	ENSP00000446771.1

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

African (AFR) AF: 0.475 AC: 19705 AN: 41472

American (AMR) AF: 0.685 AC: 10458 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2344 AN: 3470

East Asian (EAS) AF: 0.557 AC: 2877 AN: 5168

South Asian (SAS) AF: 0.811 AC: 3917 AN: 4830

European-Finnish (FIN) AF: 0.657 AC: 6952 AN: 10582

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46419 AN: 67956

Other (OTH) AF: 0.628 AC: 1327 AN: 2114

Alfa AF: 0.668 Hom.: 57300

Bravo AF: 0.618

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.78
PhyloP100		-0.14
PromoterAI		0.046	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs640081; hg19: chr12-50290554;