chr1-222750009-A-G

Variant names:

• chr1-222750009-A-G
• rs6683071
• NM_001394345.1:c.428A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 46 publications found

Genes affected

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

ENSG00000287684 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394345.1. 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
	FAM177B	NM_001394345.1	MANE Select	c.428A>G	p.Gln143Arg	missense	Exon 6 of 6	NP_001381274.1	A6PVY3-1
	FAM177B	NM_001324080.2		c.428A>G	p.Gln143Arg	missense	Exon 5 of 5	NP_001311009.1	A6PVY3-1
	FAM177B	NM_207468.3		c.428A>G	p.Gln143Arg	missense	Exon 6 of 6	NP_997351.2	A6PVY3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM177B	ENST00000445590.4	TSL:5 MANE Select	c.428A>G	p.Gln143Arg	missense	Exon 6 of 6	ENSP00000414451.2	A6PVY3-1
	FAM177B	ENST00000360827.6	TSL:5	c.428A>G	p.Gln143Arg	missense	Exon 6 of 6	ENSP00000354070.2	A6PVY3-1
	FAM177B	ENST00000893418.1		c.428A>G	p.Gln143Arg	missense	Exon 5 of 5	ENSP00000563477.1

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

GnomAD2 exomes AF: 0.806 AC: 200815 AN: 249298 AF XY: 0.802

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 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

African (AFR) AF: 0.764 AC: 25577 AN: 33464

American (AMR) AF: 0.850 AC: 38000 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 19192 AN: 26130

East Asian (EAS) AF: 0.817 AC: 32446 AN: 39696

South Asian (SAS) AF: 0.776 AC: 66950 AN: 86248

European-Finnish (FIN) AF: 0.801 AC: 42765 AN: 53420

Middle Eastern (MID) AF: 0.744 AC: 4272 AN: 5744

European-Non Finnish (NFE) AF: 0.816 AC: 907692 AN: 1111756

Other (OTH) AF: 0.794 AC: 47955 AN: 60386

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

African (AFR) AF: 0.768 AC: 31838 AN: 41466

American (AMR) AF: 0.839 AC: 12815 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2519 AN: 3468

East Asian (EAS) AF: 0.796 AC: 4094 AN: 5146

South Asian (SAS) AF: 0.770 AC: 3704 AN: 4812

European-Finnish (FIN) AF: 0.797 AC: 8430 AN: 10576

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55461 AN: 67994

Other (OTH) AF: 0.776 AC: 1641 AN: 2116

Alfa AF: 0.809 Hom.: 225754

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 v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.66	N
PhyloP100		-2.4
PrimateAI	Benign	0.18	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.037
Sift	Benign	1.0	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.010
MPC		0.17
ClinPred		0.023	T
GERP RS		-11
Varity_R		0.025
gMVP		0.031
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: rs6683071; hg19: chr1-222923351; COSMIC: COSV62600980; COSMIC: COSV62600980;