Genetic Variant FAM171B:p.Pro250Ser (chr2-186751157-C-T) – 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.748C>T(p.Pro250Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00171 in 1,605,266 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 27 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 17 hom. )

Consequence

FAM171B
NM_177454.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.82

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=0.010239631).

BP6

Variant 2-186751157-C-T is Benign according to our data. Variant chr2-186751157-C-T is described in ClinVar as [Benign]. Clinvar id is 791879.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 = 0.0096 (1461/152158) while in subpopulation AFR AF= 0.0333 (1382/41516). AF 95% confidence interval is 0.0318. There are 27 homozygotes in gnomad4. There are 720 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171B	NM_177454.4 link	c.748C>T	p.Pro250Ser	missense_variant	Exon 5 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.748C>T	p.Pro250Ser	missense_variant	Exon 5 of 8	1	NM_177454.4	ENSP00000304108.5		Q6P995-1

Frequencies

GnomAD3 genomes

AF:

0.00956

AC:

1453

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00228

AC:

570

AN:

249542

Hom.:

AF XY:

0.00176

AC XY:

238

AN XY:

134906

show subpopulations

Gnomad AFR exome

AF:

0.0316

Gnomad AMR exome

AF:

0.000997

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.000886

AC:

1287

AN:

1453108

Hom.:

Cov.:

AF XY:

0.000742

AC XY:

536

AN XY:

722628

show subpopulations

Gnomad4 AFR exome

AF:

0.0311

Gnomad4 AMR exome

AF:

0.00131

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000941

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000334

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00960

AC:

1461

AN:

152158

Hom.:

Cov.:

AF XY:

0.00968

AC XY:

720

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.0102

ESP6500AA

AF:

0.0309

AC:

136

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00307

AC:

373

Asia WGS

AF:

0.00173

AC:

AN:

3478

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

- -

Jul 23, 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

0.30

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.46

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.95

MVP

0.78

MPC

0.95

ClinPred

0.020

GERP RS

5.5

Varity_R

0.57

gMVP

0.86

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