NM_017693.4:c.1430C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017693.4(BIVM):c.1430C>T(p.Ser477Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,614,116 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 11 hom. )

Consequence

BIVM
NM_017693.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.18

Publications

7 publications found

Variant links:

Genes affected

BIVM (HGNC:16034): (basic, immunoglobulin-like variable motif containing) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

BIVM links:

BIVM-ERCC5 (HGNC:43690): (BIVM-ERCC5 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BIVM (basic, immunoglobulin-like variable motif containing) and ERCC5 (excision repair cross-complementing rodent repair deficiency, complementation group 5) genes on chromosome 13. The read-through transcript encodes a fusion protein that shares sequence identity with the products of each individual gene. [provided by RefSeq, Feb 2011]

BIVM-ERCC5 links:

ENSG00000305730 (HGNC:):

ENSG00000305730 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003577888).

BP6

Variant 13-102839783-C-T is Benign according to our data. Variant chr13-102839783-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1335133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIVM	NM_017693.4 link	c.1430C>T	p.Ser477Leu	missense_variant	Exon 11 of 11	ENST00000257336.6	NP_060163.2	Q86UB2-1
BIVM-ERCC5	NM_001204425.2 link	c.1430C>T	p.Ser477Leu	missense_variant	Exon 9 of 23		NP_001191354.2	R4GMW8Q59FZ7
BIVM	NM_001159596.2 link	c.764C>T	p.Ser255Leu	missense_variant	Exon 9 of 9		NP_001153068.1	Q86UB2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BIVM	ENST00000257336.6 link	c.1430C>T	p.Ser477Leu	missense_variant	Exon 11 of 11	1	NM_017693.4	ENSP00000257336.1	Q86UB2-1
BIVM-ERCC5	ENST00000639435.1 link	c.1430C>T	p.Ser477Leu	missense_variant	Exon 11 of 25	5		ENSP00000491742.1	R4GMW8
BIVM-ERCC5	ENST00000639132.1 link	c.743C>T	p.Ser248Leu	missense_variant	Exon 10 of 24	5		ENSP00000492684.1	A0A1W2PS85

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

299

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00177

AC:

445

AN:

251404

AF XY:

0.00170

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00335

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00271

AC:

3965

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

1936

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.000358

AC:

AN:

33478

American (AMR)

AF:

0.000425

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000487

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00338

AC:

3763

AN:

1112012

Other (OTH)

AF:

0.00184

AC:

111

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

249

498

747

996

1245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00196

AC:

299

AN:

152230

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

115

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41540

American (AMR)

AF:

0.000915

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00375

AC:

255

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00199

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00198

AC:

240

EpiCase

AF:

0.00294

EpiControl

AF:

0.00207

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BIVM: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.038

T;.;.;.;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.79

T;T;T;T;.

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0036

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.;.;.

PhyloP100

1.2

PROVEAN

Benign

-1.6

N;N;.;.;.

REVEL

Benign

0.018

Sift

Benign

0.20

T;T;.;.;.

Sift4G

Benign

0.22

T;T;.;.;.

Polyphen

0.0010

B;B;.;.;.

Vest4

0.11

MVP

0.10

MPC

0.24

ClinPred

0.010

GERP RS

3.7

Varity_R

0.060

gMVP

0.23

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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NM_017693.4:c.1430C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over