NM_017693.4:c.1430C>T

Variant names:

• chr13-102839783-C-T
• rs139012037
• NM_017693.4:c.1430C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong 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. 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.18
• Publications: 7 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]

ENSG00000305730 (HGNC:):

ACMG classification

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 VariationId is 1335133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017693.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIVM	NM_017693.4	MANE Select	c.1430C>T	p.Ser477Leu	missense	Exon 11 of 11	NP_060163.2
	BIVM-ERCC5	NM_001204425.2		c.1430C>T	p.Ser477Leu	missense	Exon 9 of 23	NP_001191354.2
	BIVM	NM_001159596.2		c.764C>T	p.Ser255Leu	missense	Exon 9 of 9	NP_001153068.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIVM	ENST00000257336.6	TSL:1 MANE Select	c.1430C>T	p.Ser477Leu	missense	Exon 11 of 11	ENSP00000257336.1
	BIVM-ERCC5	ENST00000639435.1	TSL:5	c.1430C>T	p.Ser477Leu	missense	Exon 11 of 25	ENSP00000491742.1
	BIVM-ERCC5	ENST00000639132.1	TSL:5	c.743C>T	p.Ser248Leu	missense	Exon 10 of 24	ENSP00000492684.1

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

GnomAD2 exomes AF: 0.00177 AC: 445 AN: 251404 AF XY: 0.00170

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

African (AFR) AF: 0.000358 AC: 12 AN: 33478

American (AMR) AF: 0.000425 AC: 19 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 28 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.000487 AC: 26 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00338 AC: 3763 AN: 1112012

Other (OTH) AF: 0.00184 AC: 111 AN: 60396

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

African (AFR) AF: 0.000481 AC: 20 AN: 41540

American (AMR) AF: 0.000915 AC: 14 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00375 AC: 255 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00278 Hom.: 1

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

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.2
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.018
Sift	Benign	0.20	T
Sift4G	Benign	0.22	T
Polyphen		0.0010	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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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