Genetic Variant BIVM:p.Asn234Asn (chr13-102821743-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_017693.4(BIVM):c.702C>T(p.Asn234Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

BIVM
NM_017693.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00002016

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0150

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=-0.015 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIVM	NM_017693.4 link	c.702C>T	p.Asn234Asn	splice_region_variant, synonymous_variant	Exon 6 of 11	ENST00000257336.6	NP_060163.2	Q86UB2-1
BIVM-ERCC5	NM_001204425.2 link	c.702C>T	p.Asn234Asn	splice_region_variant, synonymous_variant	Exon 4 of 23		NP_001191354.2	R4GMW8Q59FZ7
BIVM	NM_001159596.2 link	c.15C>T	p.Asn5Asn	splice_region_variant, synonymous_variant	Exon 4 of 9		NP_001153068.1	Q86UB2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BIVM	ENST00000257336.6 link	c.702C>T	p.Asn234Asn	splice_region_variant, synonymous_variant	Exon 6 of 11	1	NM_017693.4	ENSP00000257336.1	Q86UB2-1
BIVM-ERCC5	ENST00000639435.1 link	c.702C>T	p.Asn234Asn	splice_region_variant, synonymous_variant	Exon 6 of 25	5		ENSP00000491742.1	R4GMW8
BIVM-ERCC5	ENST00000639132.1 link	c.15C>T	p.Asn5Asn	splice_region_variant, synonymous_variant	Exon 5 of 24	5		ENSP00000492684.1	A0A1W2PS85

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249326

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134692

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459822

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.5

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over