2-186751157-C-T

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

5
6
7

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]

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
FAM171BNM_177454.4 linkc.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
FAM171BENST00000304698.10 linkc.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.:
28
Cov.:
32
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.:
11
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.:
17
Cov.:
30
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.:
27
Cov.:
32
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.:
5
Bravo
AF:
0.0102
ESP6500AA
AF:
0.0309
AC:
136
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00307
AC:
373
Asia WGS
AF:
0.00173
AC:
6
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
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.27
T
Eigen
Pathogenic
0.75
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.88
D
MetaRNN
Benign
0.010
T
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-5.2
D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0050
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.95
MVP
0.78
MPC
0.95
ClinPred
0.020
T
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.

Other links and lift over

dbSNP: rs79964543; hg19: chr2-187615884; API