rs1027711

chr12-49894249-A-Gchr12-49894249-A-T

Variant summary

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

The NM_012306.4(FAIM2):c.434+2782T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,232 control chromosomes in the GnomAD database, including 1,087 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 0.11 (1087 hom., cov: 32)
• Consequence: FAIM2 NM_012306.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAIM2	NM_012306.4	c.434+2782T>C		intron_variant		ENST00000320634.8
FAIM2	XM_005268730.4	c.308+2782T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAIM2	ENST00000320634.8	c.434+2782T>C		intron_variant		1	NM_012306.4	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16760 AN: 152114 Hom.: 1083 Cov.: 32

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.0519

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.110 AC: 16775 AN: 152232 Hom.: 1087 Cov.: 32 AF XY: 0.105 AC XY: 7817 AN XY: 74434

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.0807

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.0125

Gnomad4 SAS AF: 0.0511

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.123

Alfa AF: 0.138 Hom.: 1477

Bravo AF: 0.107

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.3
Dann	Benign	0.60

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: rs1027711; hg19: chr12-50288032;