chr17-75724761-G-C

Variant names:

• chr17-75724761-G-C
• rs751173051
• NM_000213.5:c.58G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000213.5(ITGB4):​c.58G>C​(p.Val20Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ITGB4 NM_000213.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

Genes affected

ITGB4 (HGNC:6158): (integrin subunit beta 4) Integrins are heterodimers comprised of alpha and beta subunits, that are noncovalently associated transmembrane glycoprotein receptors. Different combinations of alpha and beta polypeptides form complexes that vary in their ligand-binding specificities. Integrins mediate cell-matrix or cell-cell adhesion, and transduced signals that regulate gene expression and cell growth. This gene encodes the integrin beta 4 subunit, a receptor for the laminins. This subunit tends to associate with alpha 6 subunit and is likely to play a pivotal role in the biology of invasive carcinoma. Mutations in this gene are associated with epidermolysis bullosa with pyloric atresia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092696935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB4	NM_000213.5	c.58G>C	p.Val20Leu	missense_variant	Exon 2 of 40	ENST00000200181.8	NP_000204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB4	ENST00000200181.8	c.58G>C	p.Val20Leu	missense_variant	Exon 2 of 40	1	NM_000213.5	ENSP00000200181.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461348 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726988

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.19
DANN	Benign	0.88
DEOGEN2	Benign	0.049	.;T;.;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.48	.;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.093	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.81	L;L;L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.22	.;N;.;N
REVEL	Benign	0.066
Sift	Benign	0.26	.;T;.;T
Sift4G	Benign	0.59	T;T;T;T
Polyphen		0.048, 0.0080	.;B;.;B
Vest4		0.11
MutPred		0.48		Loss of MoRF binding (P = 0.0954);Loss of MoRF binding (P = 0.0954);Loss of MoRF binding (P = 0.0954);Loss of MoRF binding (P = 0.0954);
MVP		0.66
MPC		0.28
ClinPred		0.13	T
GERP RS		1.3
Varity_R		0.044
gMVP		0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs751173051; hg19: chr17-73720841;