chr12-49903887-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAIM2	NM_012306.4	MANE Select	c.-95A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_036438.2
	FAIM2	NM_012306.4	MANE Select	c.-95A>G		5_prime_UTR	Exon 1 of 12	NP_036438.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAIM2	ENST00000320634.8	TSL:1 MANE Select	c.-95A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000321951.3	Q9BWQ8-1
	FAIM2	ENST00000320634.8	TSL:1 MANE Select	c.-95A>G		5_prime_UTR	Exon 1 of 12	ENSP00000321951.3	Q9BWQ8-1
	FAIM2	ENST00000947305.1		c.-95A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000617364.1

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

African (AFR) AF: 0.238 AC: 6047 AN: 25458

American (AMR) AF: 0.498 AC: 11904 AN: 23914

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 13414 AN: 18604

East Asian (EAS) AF: 0.361 AC: 11521 AN: 31942

South Asian (SAS) AF: 0.741 AC: 46780 AN: 63142

European-Finnish (FIN) AF: 0.596 AC: 26058 AN: 43752

Middle Eastern (MID) AF: 0.675 AC: 2325 AN: 3444

European-Non Finnish (NFE) AF: 0.592 AC: 550003 AN: 928914

Other (OTH) AF: 0.576 AC: 28819 AN: 50012

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

African (AFR) AF: 0.249 AC: 10324 AN: 41492

American (AMR) AF: 0.505 AC: 7713 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2560 AN: 3466

East Asian (EAS) AF: 0.340 AC: 1749 AN: 5138

South Asian (SAS) AF: 0.733 AC: 3537 AN: 4824

European-Finnish (FIN) AF: 0.602 AC: 6371 AN: 10590

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40151 AN: 67940

Other (OTH) AF: 0.537 AC: 1134 AN: 2112

Alfa AF: 0.558 Hom.: 93204

Bravo AF: 0.465

Asia WGS AF: 0.553 AC: 1919 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.90
PhyloP100		2.3
PromoterAI		-0.13	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

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

Other links and lift over

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