13-101567699-G-A

Position:

• chr13-101567699-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004791.3(ITGBL1):​c.317G>A​(p.Gly106Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00257 in 1,612,318 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (42 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (55 hom.)
• Consequence: ITGBL1 NM_004791.3 missense, splice_region
• Scores: Splicing: ADA: 0.9996
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.89

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 13-101567699-G-A is Benign according to our data. Variant chr13-101567699-G-A is described in ClinVar as [Benign]. Clinvar id is 790681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2125/152144) while in subpopulation AFR AF= 0.0481 (1996/41524). AF 95% confidence interval is 0.0463. There are 42 homozygotes in gnomad4. There are 979 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGBL1	NM_004791.3	c.317G>A	p.Gly106Asp	missense_variant, splice_region_variant	3/11	ENST00000376180.8
ITGBL1	NM_001271756.2	c.38G>A	p.Gly13Asp	missense_variant, splice_region_variant	2/10
ITGBL1	NM_001271754.2	c.-107G>A		splice_region_variant, 5_prime_UTR_variant	2/11
ITGBL1	NM_001271755.2	c.317-7725G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGBL1	ENST00000376180.8	c.317G>A	p.Gly106Asp	missense_variant, splice_region_variant	3/11	1	NM_004791.3	P1
ITGBL1	ENST00000618057.4	c.317-7725G>A		intron_variant		1
ITGBL1	ENST00000376162.7	c.38G>A	p.Gly13Asp	missense_variant, splice_region_variant	2/10	2
ITGBL1	ENST00000545560.6	c.-107G>A		splice_region_variant, 5_prime_UTR_variant	2/11	2

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 2120 AN: 152026 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00558

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00363 AC: 906 AN: 249772 Hom.: 16 AF XY: 0.00255 AC XY: 344 AN XY: 134928

Gnomad AFR exome AF: 0.0490

Gnomad AMR exome AF: 0.00233

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000658

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00246

GnomAD4 exome AF: 0.00138 AC: 2013 AN: 1460174 Hom.: 55 Cov.: 30 AF XY: 0.00118 AC XY: 858 AN XY: 726432

Gnomad4 AFR exome AF: 0.0471

Gnomad4 AMR exome AF: 0.00285

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000581

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000855

Gnomad4 OTH exome AF: 0.00333

GnomAD4 genome AF: 0.0140 AC: 2125 AN: 152144 Hom.: 42 Cov.: 32 AF XY: 0.0132 AC XY: 979 AN XY: 74390

Gnomad4 AFR AF: 0.0481

Gnomad4 AMR AF: 0.00557

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00205 Hom.: 6

Bravo AF: 0.0159

ESP6500AA AF: 0.0495 AC: 218

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00464 AC: 563

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000219

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0080	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0021	T
MetaSVM	Uncertain	0.20	D
MutationTaster	Benign	1.0	D;D;D
Sift4G	Benign	0.072	T
Vest4		0.077
MVP		0.48
ClinPred		0.023	T
GERP RS		5.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.87
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

Publications

LitVar

Other links and lift over

dbSNP: rs62637618; hg19: chr13-102220050; COSMIC: COSV99058498;