13-102839783-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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. 13/19 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

Genes affected

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

BIVM-ERCC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIVM	NM_017693.4	c.1430C>T	p.Ser477Leu	missense_variant	11/11	ENST00000257336.6
BIVM-ERCC5	NM_001204425.2	c.1430C>T	p.Ser477Leu	missense_variant	9/23
BIVM	NM_001159596.2	c.764C>T	p.Ser255Leu	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIVM	ENST00000257336.6	c.1430C>T	p.Ser477Leu	missense_variant	11/11	1	NM_017693.4	P1

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 299 AN: 152112 Hom.: 1 Cov.: 32

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

GnomAD3 exomes AF: 0.00177 AC: 445 AN: 251404 Hom.: 3 AF XY: 0.00170 AC XY: 231 AN XY: 135866

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 SAS exome AF: 0.0000327

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.: 11 Cov.: 31 AF XY: 0.00266 AC XY: 1936 AN XY: 727242

Gnomad4 AFR exome AF: 0.000358

Gnomad4 AMR exome AF: 0.000425

Gnomad4 ASJ exome AF: 0.00107

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000487

Gnomad4 NFE exome AF: 0.00338

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00196 AC: 299 AN: 152230 Hom.: 1 Cov.: 32 AF XY: 0.00155 AC XY: 115 AN XY: 74418

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.00375

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00305 Hom.: 0

Bravo AF: 0.00199

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00291 AC: 25

ExAC AF: 0.00198 AC: 240

EpiCase AF: 0.00294

EpiControl AF: 0.00207

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

BIVM: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Benign	0.038	T;.;.;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.79	T;T;T;T;.
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.0036	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;.;.;.
MutationTaster	Benign	1.0	N;N;N
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	T
GERP RS		3.7
Varity_R		0.060
gMVP		0.23

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

LitVar

Other links and lift over

dbSNP: rs139012037; hg19: chr13-103492133; COSMIC: COSV57279650;