dbSNP rs79964543: FAM171B:p.Pro250Ser (chr2-186751157-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177454.4. 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
	FAM171B	NM_177454.4	MANE Select	c.748C>T	p.Pro250Ser	missense	Exon 5 of 8	NP_803237.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM171B	ENST00000304698.10	TSL:1 MANE Select	c.748C>T	p.Pro250Ser	missense	Exon 5 of 8	ENSP00000304108.5	Q6P995-1
	FAM171B	ENST00000909200.1		c.799C>T	p.Pro267Ser	missense	Exon 6 of 9	ENSP00000579259.1

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

GnomAD2 exomes

AF:

0.00228

AC:

570

AN:

249542

AF XY:

0.00176

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 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

African (AFR)

AF:

0.0311

AC:

1035

AN:

33296

American (AMR)

AF:

0.00131

AC:

AN:

44312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25728

East Asian (EAS)

AF:

0.00

AC:

AN:

39564

South Asian (SAS)

AF:

0.0000941

AC:

AN:

85050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52994

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.0000334

AC:

AN:

1106494

Other (OTH)

AF:

0.00239

AC:

143

AN:

59950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

117

176

234

293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00960

AC:

1461

AN:

152158

Hom.:

Cov.:

AF XY:

0.00968

AC XY:

720

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0333

AC:

1382

AN:

41516

American (AMR)

AF:

0.00379

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67986

Other (OTH)

AF:

0.00614

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

147

220

294

367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00350

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

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

PhyloP100

5.8

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

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over