13-102821743-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017693.4(BIVM):​c.702C>G​(p.Asn234Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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)
• Consequence: BIVM NM_017693.4 missense, splice_region
• Scores: Splicing: ADA: 0.00002259
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.148581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIVM	NM_017693.4	c.702C>G	p.Asn234Lys	missense_variant, splice_region_variant	Exon 6 of 11	ENST00000257336.6	NP_060163.2
BIVM-ERCC5	NM_001204425.2	c.702C>G	p.Asn234Lys	missense_variant, splice_region_variant	Exon 4 of 23		NP_001191354.2
BIVM	NM_001159596.2	c.15C>G	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>G	p.Asn234Lys	missense_variant, splice_region_variant	Exon 6 of 11	1	NM_017693.4	ENSP00000257336.1
BIVM-ERCC5	ENST00000639435.1	c.702C>G	p.Asn234Lys	missense_variant, splice_region_variant	Exon 6 of 25	5		ENSP00000491742.1
BIVM-ERCC5	ENST00000639132.1	c.15C>G	p.Asn5Lys	missense_variant, splice_region_variant	Exon 5 of 24	5		ENSP00000492684.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T;.;.;.;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.82
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.88	D;D;D;D;.
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.;.;.
PROVEAN	Uncertain	-2.7	D;N;.;.;.
REVEL	Benign	0.065
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		0.47	T
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.098
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-103474093;