rs706795

Variant names:

• chr12-49903887-T-C
• rs706795
• NM_012306.4:c.-95A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012306.4(FAIM2):​c.-95A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,341,232 control chromosomes in the GnomAD database, including 227,484 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 0.49 (20127 hom., cov: 33)
  • Exomes 𝑓: 0.59 (207357 hom.)
• Consequence: FAIM2 NM_012306.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32

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]

LINC02395 (HGNC:53322): (long intergenic non-protein coding RNA 2395)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAIM2	NM_012306.4	c.-95A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	ENST00000320634.8	NP_036438.2
FAIM2	NM_012306.4	c.-95A>G		5_prime_UTR_variant	Exon 1 of 12	ENST00000320634.8	NP_036438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAIM2	ENST00000320634.8	c.-95A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	1	NM_012306.4	ENSP00000321951.3
FAIM2	ENST00000320634.8	c.-95A>G		5_prime_UTR_variant	Exon 1 of 12	1	NM_012306.4	ENSP00000321951.3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74246 AN: 151934 Hom.: 20134 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.586 AC: 696871 AN: 1189182 Hom.: 207357 Cov.: 16 AF XY: 0.591 AC XY: 345715 AN XY: 584918

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.721

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.741

Gnomad4 FIN exome AF: 0.596

Gnomad4 NFE exome AF: 0.592

Gnomad4 OTH exome AF: 0.576

GnomAD4 genome AF: 0.488 AC: 74239 AN: 152050 Hom.: 20127 Cov.: 33 AF XY: 0.494 AC XY: 36750 AN XY: 74330

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.537

Alfa AF: 0.574 Hom.: 43368

Bravo AF: 0.465

Asia WGS AF: 0.553 AC: 1919 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs706795; hg19: chr12-50297670; COSMIC: COSV57739822; COSMIC: COSV57739822;