Genetic Variant FAM171B:p.Arg95His (chr2-186740273-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_177454.4(FAM171B):c.284G>A(p.Arg95His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00635 in 1,613,918 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 35 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 47 hom. )

Consequence

FAM171B
NM_177454.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.94

Variant links:

Genes affected

FAM171B (HGNC:29412): (family with sequence similarity 171 member B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM171B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044664145).

BP6

Variant 2-186740273-G-A is Benign according to our data. Variant chr2-186740273-G-A is described in ClinVar as [Benign]. Clinvar id is 777369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2026/152198) while in subpopulation AFR AF= 0.035 (1452/41516). AF 95% confidence interval is 0.0335. There are 35 homozygotes in gnomad4. There are 971 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171B	NM_177454.4 link	c.284G>A	p.Arg95His	missense_variant	Exon 2 of 8	ENST00000304698.10	NP_803237.3	Q6P995-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM171B	ENST00000304698.10 link	c.284G>A	p.Arg95His	missense_variant	Exon 2 of 8	1	NM_177454.4	ENSP00000304108.5		Q6P995-1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2022

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00622

Gnomad FIN

AF:

0.00878

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00422

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00723

AC:

1818

AN:

251348

Hom.:

AF XY:

0.00681

AC XY:

925

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.0366

Gnomad AMR exome

AF:

0.00564

Gnomad ASJ exome

AF:

0.00486

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.00585

Gnomad FIN exome

AF:

0.00989

Gnomad NFE exome

AF:

0.00467

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.00562

AC:

8219

AN:

1461720

Hom.:

Cov.:

AF XY:

0.00566

AC XY:

4115

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0371

Gnomad4 AMR exome

AF:

0.00566

Gnomad4 ASJ exome

AF:

0.00478

Gnomad4 EAS exome

AF:

0.00121

Gnomad4 SAS exome

AF:

0.00625

Gnomad4 FIN exome

AF:

0.00848

Gnomad4 NFE exome

AF:

0.00455

Gnomad4 OTH exome

AF:

0.00724

GnomAD4 genome

AF:

0.0133

AC:

2026

AN:

152198

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

971

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0350

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.00878

Gnomad4 NFE

AF:

0.00422

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00654

Hom.:

Bravo

AF:

0.0149

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.0354

AC:

156

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00764

AC:

927

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00447

EpiControl

AF:

0.00599

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Uncertain

DANN

Benign

0.84

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.021

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.85

T;D

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.36

N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

1.0

N;.

REVEL

Benign

0.045

Sift

Benign

0.53

T;.

Sift4G

Benign

0.35

T;T

Polyphen

0.037

B;.

Vest4

0.11

MVP

0.31

MPC

0.33

ClinPred

0.011

GERP RS

5.3

Varity_R

0.021

gMVP

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over