rs1421267796

Variant names:

• chr13-101575497-G-C
• rs1421267796
• NM_004791.3:c.537G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-101575497-G-C
• chr13-101575497-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004791.3(ITGBL1):​c.537G>C​(p.Glu179Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,496 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• Publications: 1 publications found

Genes affected

ITGBL1 (HGNC:6164): (integrin subunit beta like 1) This gene encodes a beta integrin-related protein that is a member of the EGF-like protein family. The encoded protein contains integrin-like cysteine-rich repeats. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.537G>C	p.Glu179Asp	missense_variant	Exon 4 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.390G>C	p.Glu130Asp	missense_variant	Exon 3 of 10		NP_001258684.1
ITGBL1	NM_001271756.2	c.258G>C	p.Glu86Asp	missense_variant	Exon 3 of 10		NP_001258685.1
ITGBL1	NM_001271754.2	c.114G>C	p.Glu38Asp	missense_variant	Exon 3 of 11		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.537G>C	p.Glu179Asp	missense_variant	Exon 4 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.390G>C	p.Glu130Asp	missense_variant	Exon 3 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000376162.7	c.258G>C	p.Glu86Asp	missense_variant	Exon 3 of 10	2		ENSP00000365332.3
ITGBL1	ENST00000545560.6	c.114G>C	p.Glu38Asp	missense_variant	Exon 3 of 11	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460496 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726648

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110964

Other (OTH) AF: 0.00 AC: 0 AN: 60308

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T;T;T;.;.
Eigen	Benign	0.090
Eigen_PC	Benign	0.059
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D;D;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.47	T;T;T;T;T
MetaSVM	Uncertain	0.77	D
MutationAssessor	Uncertain	2.7	.;M;.;.;.
PhyloP100		0.41
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.47	.;N;.;N;N
REVEL	Uncertain	0.56
Sift	Benign	0.068	.;T;.;D;D
Sift4G	Uncertain	0.058	T;T;T;T;T
Polyphen		1.0	.;D;.;.;.
Vest4		0.62
MutPred		0.37		.;Gain of catalytic residue at K176 (P = 0.0082);.;.;.;
MVP		0.69
MPC		0.72
ClinPred		0.75	D
GERP RS		1.5
Varity_R		0.10
gMVP		0.59
Mutation Taster		=45/55	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1421267796; hg19: chr13-102227848;