rs2048200314

Variant names:

• chr13-101453941-G-A
• rs2048200314
• NM_004791.3:c.157G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-101453941-G-A
• chr13-101453941-G-C
• chr13-101453941-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004791.3(ITGBL1):​c.157G>A​(p.Ala53Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000316 in 1,266,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A53P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34166092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3	c.157G>A	p.Ala53Thr	missense_variant	Exon 2 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.157G>A	p.Ala53Thr	missense_variant	Exon 2 of 10		NP_001258684.1
ITGBL1	NM_001271754.2	c.-108+1010G>A		intron_variant	Intron 1 of 10		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8	c.157G>A	p.Ala53Thr	missense_variant	Exon 2 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.157G>A	p.Ala53Thr	missense_variant	Exon 2 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000545560.6	c.-108+1010G>A		intron_variant	Intron 1 of 10	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000316 AC: 4 AN: 1266270 Hom.: 0 Cov.: 33 AF XY: 0.00000482 AC XY: 3 AN XY: 622042

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

African (AFR) AF: 0.00 AC: 0 AN: 25708

American (AMR) AF: 0.00 AC: 0 AN: 21084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20484

East Asian (EAS) AF: 0.0000356 AC: 1 AN: 28072

South Asian (SAS) AF: 0.00 AC: 0 AN: 60148

European-Finnish (FIN) AF: 0.0000229 AC: 1 AN: 43596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4604

European-Non Finnish (NFE) AF: 0.00000198 AC: 2 AN: 1011308

Other (OTH) AF: 0.00 AC: 0 AN: 51266

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.065834), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0022	T;T
Eigen	Benign	-0.038
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.54	T;T
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.4	.;L
PhyloP100		4.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.19	.;N
REVEL	Benign	0.24
Sift	Benign	0.40	.;T
Sift4G	Benign	0.68	T;T
Polyphen		0.14	.;B
Vest4		0.43
MutPred		0.32		Gain of catalytic residue at P57 (P = 0);Gain of catalytic residue at P57 (P = 0);
MVP		0.68
MPC		0.19
ClinPred		0.79	D
GERP RS		5.4
Varity_R		0.16
gMVP		0.19
Mutation Taster		=88/12	polymorphism

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: rs2048200314; hg19: chr13-102106292;