NM_012306.4:c.435-1158C>T

Variant names:

• chr12-49892272-G-A
• rs905619
• NM_012306.4:c.435-1158C>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.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
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 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.435-1158C>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.435-1158C>T		intron	N/A	ENSP00000321951.3
	FAIM2	ENST00000550890.5	TSL:2	c.297-1158C>T		intron	N/A	ENSP00000450132.1
	FAIM2	ENST00000552669.5	TSL:3	c.309-1158C>T		intron	N/A	ENSP00000446771.1

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

African (AFR) AF: 0.317 AC: 13085 AN: 41284

American (AMR) AF: 0.293 AC: 4457 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2170 AN: 5134

South Asian (SAS) AF: 0.336 AC: 1617 AN: 4808

European-Finnish (FIN) AF: 0.0789 AC: 834 AN: 10574

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0581 AC: 3949 AN: 67942

Other (OTH) AF: 0.161 AC: 340 AN: 2110

Alfa AF: 0.104 Hom.: 5340

Bravo AF: 0.200

Asia WGS AF: 0.362 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.53
PhyloP100		0.44
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: rs905619; hg19: chr12-50286055;