1-222750009-A-G

Position:

• chr1-222750009-A-G

Variant summary

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

The NM_001394345.1(FAM177B):​c.428A>G​(p.Gln143Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 1,613,604 control chromosomes in the GnomAD database, including 529,331 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.80 (48637 hom., cov: 31)
  • Exomes 𝑓: 0.81 (480694 hom.)
• Consequence: FAM177B NM_001394345.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

Genes affected

FAM177B (HGNC:34395): (family with sequence similarity 177 member B)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.036132E-7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM177B	NM_001394345.1	c.428A>G	p.Gln143Arg	missense_variant	6/6	ENST00000445590.4	NP_001381274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM177B	ENST00000445590.4	c.428A>G	p.Gln143Arg	missense_variant	6/6	5	NM_001394345.1	ENSP00000414451	P1
	ENST00000654074.1	n.287-3113T>C		intron_variant, non_coding_transcript_variant
FAM177B	ENST00000360827.6	c.428A>G	p.Gln143Arg	missense_variant	6/6	5		ENSP00000354070	P1
FAM177B	ENST00000391880.6	c.*569A>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000375752

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121368 AN: 151948 Hom.: 48591 Cov.: 31

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.777

GnomAD3 exomes AF: 0.806 AC: 200815 AN: 249298 Hom.: 81184 AF XY: 0.802 AC XY: 108507 AN XY: 135238

Gnomad AFR exome AF: 0.764

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.726

Gnomad EAS exome AF: 0.785

Gnomad SAS exome AF: 0.774

Gnomad FIN exome AF: 0.801

Gnomad NFE exome AF: 0.817

Gnomad OTH exome AF: 0.777

GnomAD4 exome AF: 0.811 AC: 1184849 AN: 1461538 Hom.: 480694 Cov.: 48 AF XY: 0.809 AC XY: 588369 AN XY: 727090

Gnomad4 AFR exome AF: 0.764

Gnomad4 AMR exome AF: 0.850

Gnomad4 ASJ exome AF: 0.734

Gnomad4 EAS exome AF: 0.817

Gnomad4 SAS exome AF: 0.776

Gnomad4 FIN exome AF: 0.801

Gnomad4 NFE exome AF: 0.816

Gnomad4 OTH exome AF: 0.794

GnomAD4 genome AF: 0.799 AC: 121471 AN: 152066 Hom.: 48637 Cov.: 31 AF XY: 0.799 AC XY: 59360 AN XY: 74318

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.776

Alfa AF: 0.808 Hom.: 123019

Bravo AF: 0.800

TwinsUK AF: 0.810 AC: 3003

ALSPAC AF: 0.830 AC: 3199

ESP6500AA AF: 0.767 AC: 3039

ESP6500EA AF: 0.810 AC: 6775

ExAC AF: 0.803 AC: 97041

Asia WGS AF: 0.762 AC: 2648 AN: 3478

EpiCase AF: 0.809

EpiControl AF: 0.810

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.023
DANN	Benign	0.62
DEOGEN2	Benign	0.0084	T;T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.092	.;T
MetaRNN	Benign	9.0e-7	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.66	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.18	T
PROVEAN	Benign	0.25	N;N
REVEL	Benign	0.037
Sift	Benign	1.0	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.0	B;B
Vest4		0.010
MPC		0.17
ClinPred		0.023	T
GERP RS		-11
Varity_R		0.025
gMVP		0.031

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: rs6683071; hg19: chr1-222923351; COSMIC: COSV62600980; COSMIC: COSV62600980;