chr13-101453932-C-A

Variant names:

• chr13-101453932-C-A
• rs982820653
• NM_004791.3:c.148C>A

Variant summary

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

The NM_004791.3(ITGBL1):​c.148C>A​(p.Arg50Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,240,946 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R50G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ITGBL1 NM_004791.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697
• 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 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.148C>A	p.Arg50Ser	missense_variant	Exon 2 of 11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2	c.148C>A	p.Arg50Ser	missense_variant	Exon 2 of 10		NP_001258684.1
ITGBL1	NM_001271754.2	c.-108+1001C>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.148C>A	p.Arg50Ser	missense_variant	Exon 2 of 11	1	NM_004791.3	ENSP00000365351.3
ITGBL1	ENST00000618057.4	c.148C>A	p.Arg50Ser	missense_variant	Exon 2 of 10	1		ENSP00000481484.1
ITGBL1	ENST00000545560.6	c.-108+1001C>A		intron_variant	Intron 1 of 10	2		ENSP00000439903.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000161 AC: 2 AN: 1240946 Hom.: 0 Cov.: 33 AF XY: 0.00000165 AC XY: 1 AN XY: 607762

African (AFR) AF: 0.00 AC: 0 AN: 25104

American (AMR) AF: 0.00 AC: 0 AN: 17904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18838

East Asian (EAS) AF: 0.00 AC: 0 AN: 27740

South Asian (SAS) AF: 0.00 AC: 0 AN: 54412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4298

European-Non Finnish (NFE) AF: 0.00000200 AC: 2 AN: 1000688

Other (OTH) AF: 0.00 AC: 0 AN: 50166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.079
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.57	T;T
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.36	.;N
PhyloP100		0.70
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.18	.;N
REVEL	Benign	0.27
Sift	Benign	0.061	.;T
Sift4G	Uncertain	0.054	T;D
Polyphen		0.97	.;D
Vest4		0.56
MVP		0.58
MPC		0.63
ClinPred		0.92	D
GERP RS		0.42
Varity_R		0.23
gMVP		0.74
Mutation Taster		=68/32	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: rs982820653; hg19: chr13-102106283;