3-138611020-G-A

Variant names:

• chr3-138611020-G-A
• rs811322
• NM_001033031.2:c.-17+2083G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001033030.2(FAIM):​c.63G>A​(p.Pro21Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,611,770 control chromosomes in the GnomAD database, including 296,357 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 0.60 (28365 hom., cov: 32)
  • Exomes 𝑓: 0.60 (267992 hom.)
• Consequence: FAIM NM_001033030.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 28 publications found

Genes affected

FAIM (HGNC:18703): (Fas apoptotic inhibitory molecule) The protein encoded by this gene protects against death receptor-triggered apoptosis and regulates B-cell signaling and differentiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP7: Synonymous conserved (PhyloP=0.499 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033030.2. 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
	FAIM	NM_001033031.2	MANE Select	c.-17+2083G>A		intron	N/A	NP_001028203.1	Q9NVQ4-3
	FAIM	NM_001033030.2		c.63G>A	p.Pro21Pro	synonymous	Exon 2 of 6	NP_001028202.1	Q9NVQ4-2
	FAIM	NM_001033032.2		c.-23+2083G>A		intron	N/A	NP_001028204.1	Q9NVQ4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAIM	ENST00000360570.8	TSL:3 MANE Select	c.-17+2083G>A		intron	N/A	ENSP00000353775.3	Q9NVQ4-3
	FAIM	ENST00000393035.6	TSL:1	c.-23+2083G>A		intron	N/A	ENSP00000376755.2	Q9NVQ4-1
	FAIM	ENST00000338446.8	TSL:5	c.63G>A	p.Pro21Pro	synonymous	Exon 2 of 6	ENSP00000342805.4	Q9NVQ4-2

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91614 AN: 151900 Hom.: 28327 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.583

GnomAD2 exomes AF: 0.657 AC: 165200 AN: 251334 AF XY: 0.653

Gnomad AFR exome AF: 0.566

Gnomad AMR exome AF: 0.781

Gnomad ASJ exome AF: 0.506

Gnomad EAS exome AF: 0.990

Gnomad FIN exome AF: 0.694

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.622

GnomAD4 exome AF: 0.599 AC: 874658 AN: 1459754 Hom.: 267992 Cov.: 38 AF XY: 0.601 AC XY: 436860 AN XY: 726336

African (AFR) AF: 0.564 AC: 18852 AN: 33438

American (AMR) AF: 0.768 AC: 34327 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 13130 AN: 26104

East Asian (EAS) AF: 0.984 AC: 39075 AN: 39694

South Asian (SAS) AF: 0.725 AC: 62468 AN: 86206

European-Finnish (FIN) AF: 0.693 AC: 37024 AN: 53400

Middle Eastern (MID) AF: 0.561 AC: 3232 AN: 5762

European-Non Finnish (NFE) AF: 0.567 AC: 629749 AN: 1110134

Other (OTH) AF: 0.610 AC: 36801 AN: 60318

GnomAD4 genome AF: 0.603 AC: 91699 AN: 152016 Hom.: 28365 Cov.: 32 AF XY: 0.615 AC XY: 45714 AN XY: 74304

African (AFR) AF: 0.557 AC: 23067 AN: 41444

American (AMR) AF: 0.677 AC: 10341 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1746 AN: 3468

East Asian (EAS) AF: 0.985 AC: 5102 AN: 5182

South Asian (SAS) AF: 0.737 AC: 3555 AN: 4822

European-Finnish (FIN) AF: 0.700 AC: 7392 AN: 10562

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38657 AN: 67944

Other (OTH) AF: 0.588 AC: 1241 AN: 2110

Alfa AF: 0.579 Hom.: 106513

Bravo AF: 0.602

Asia WGS AF: 0.839 AC: 2915 AN: 3478

EpiCase AF: 0.568

EpiControl AF: 0.555

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.7
DANN	Benign	0.45
PhyloP100		0.50
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: rs811322; hg19: chr3-138329862; COSMIC: COSV58158463;