rs377757672

Variant names:

• chr13-102821743-C-A
• rs377757672
• NM_017693.4:c.702C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-102821743-C-A
• chr13-102821743-C-G
• chr13-102821743-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017693.4(BIVM):​c.702C>A​(p.Asn234Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,611,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: BIVM NM_017693.4 missense, splice_region
• Scores: Splicing: ADA: 0.000009770
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0150
• Publications: 2 publications found

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: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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.117587835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIVM	NM_017693.4	c.702C>A	p.Asn234Lys	missense_variant, splice_region_variant	Exon 6 of 11	ENST00000257336.6	NP_060163.2
BIVM-ERCC5	NM_001204425.2	c.702C>A	p.Asn234Lys	missense_variant, splice_region_variant	Exon 4 of 23		NP_001191354.2
BIVM	NM_001159596.2	c.15C>A	p.Asn5Lys	missense_variant, splice_region_variant	Exon 4 of 9		NP_001153068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIVM	ENST00000257336.6	c.702C>A	p.Asn234Lys	missense_variant, splice_region_variant	Exon 6 of 11	1	NM_017693.4	ENSP00000257336.1
BIVM-ERCC5	ENST00000639435.1	c.702C>A	p.Asn234Lys	missense_variant, splice_region_variant	Exon 6 of 25	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.15C>A	p.Asn5Lys	missense_variant, splice_region_variant	Exon 5 of 24	5		ENSP00000492684.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000481 AC: 12 AN: 249326 AF XY: 0.0000297

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000123 AC: 180 AN: 1459822 Hom.: 0 Cov.: 31 AF XY: 0.0000923 AC XY: 67 AN XY: 726108

African (AFR) AF: 0.0000300 AC: 1 AN: 33382

American (AMR) AF: 0.0000226 AC: 1 AN: 44246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26038

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 85662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000148 AC: 164 AN: 1111428

Other (OTH) AF: 0.000232 AC: 14 AN: 60304

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152168 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74352

African (AFR) AF: 0.0000724 AC: 3 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000793

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.702C>A (p.N234K) alteration is located in exon 6 (coding exon 4) of the BIVM gene. This alteration results from a C to A substitution at nucleotide position 702, causing the asparagine (N) at amino acid position 234 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;.;.;.;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.82
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D;D;D;D;.
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.;.;.
PhyloP100		-0.015
PROVEAN	Uncertain	-2.7	D;N;.;.;.
REVEL	Benign	0.061
Sift	Uncertain	0.015	D;D;.;.;.
Sift4G	Uncertain	0.022	D;D;.;.;.
Polyphen		0.073	B;B;.;.;.
Vest4		0.37
MutPred		0.37		Gain of catalytic residue at N234 (P = 0);.;Gain of catalytic residue at N234 (P = 0);.;Gain of catalytic residue at N234 (P = 0);
MVP		0.055
MPC		0.38
ClinPred		0.18	T
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.22
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000098
dbscSNV1_RF	Benign	0.044
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

Other links and lift over

dbSNP: rs377757672; hg19: chr13-103474093;