chr17-75724820-A-G

Variant names:

• chr17-75724820-A-G
• rs820167
• NM_000213.5:c.79+38A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000213.5(ITGB4):​c.79+38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,558,724 control chromosomes in the GnomAD database, including 772,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (72736 hom., cov: 34)
  • Exomes 𝑓: 1.0 (700036 hom.)
• Consequence: ITGB4 NM_000213.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.238
• Publications: 6 publications found

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]

ITGB4 Gene-Disease associations (from GenCC):

• epidermolysis bullosa simplex

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• junctional epidermolysis bullosa with pyloric atresia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Genomics England PanelApp
• junctional epidermolysis bullosa, non-Herlitz type

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• aplasia cutis congenita

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• epidermolysis bullosa simplex 5C, with pyloric atresia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• generalized junctional epidermolysis bullosa non-Herlitz type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• localized junctional epidermolysis bullosa, non-Herlitz type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• epidermolysis bullosa simplex 1C, localized

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-75724820-A-G is Benign according to our data. Variant chr17-75724820-A-G is described in ClinVar as Benign. ClinVar VariationId is 1227767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000213.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB4	NM_000213.5	MANE Select	c.79+38A>G		intron	N/A	NP_000204.3
	ITGB4	NM_001005619.2		c.79+38A>G		intron	N/A	NP_001005619.1
	ITGB4	NM_001005731.3		c.79+38A>G		intron	N/A	NP_001005731.1	P16144-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB4	ENST00000200181.8	TSL:1 MANE Select	c.79+38A>G		intron	N/A	ENSP00000200181.3	P16144-1
	ITGB4	ENST00000449880.7	TSL:1	c.79+38A>G		intron	N/A	ENSP00000400217.2	P16144-3
	ITGB4	ENST00000450894.7	TSL:1	c.79+38A>G		intron	N/A	ENSP00000405536.3	P16144-2

Frequencies

GnomAD3 genomes AF: 0.976 AC: 148647 AN: 152228 Hom.: 72685 Cov.: 34

Gnomad AFR AF: 0.917

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.983

GnomAD2 exomes AF: 0.994 AC: 244926 AN: 246448 AF XY: 0.996

Gnomad AFR exome AF: 0.915

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.996

GnomAD4 exome AF: 0.998 AC: 1403108 AN: 1406378 Hom.: 700036 Cov.: 23 AF XY: 0.998 AC XY: 701475 AN XY: 702860

African (AFR) AF: 0.919 AC: 29710 AN: 32342

American (AMR) AF: 0.996 AC: 44389 AN: 44560

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25760 AN: 25760

East Asian (EAS) AF: 1.00 AC: 39440 AN: 39440

South Asian (SAS) AF: 1.00 AC: 85059 AN: 85072

European-Finnish (FIN) AF: 1.00 AC: 51575 AN: 51578

Middle Eastern (MID) AF: 0.998 AC: 5649 AN: 5662

European-Non Finnish (NFE) AF: 1.00 AC: 1063345 AN: 1063446

Other (OTH) AF: 0.994 AC: 58181 AN: 58518

GnomAD4 genome AF: 0.976 AC: 148756 AN: 152346 Hom.: 72736 Cov.: 34 AF XY: 0.977 AC XY: 72814 AN XY: 74502

African (AFR) AF: 0.918 AC: 38143 AN: 41572

American (AMR) AF: 0.993 AC: 15201 AN: 15306

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 1.00 AC: 4834 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68020 AN: 68038

Other (OTH) AF: 0.983 AC: 2079 AN: 2114

Alfa AF: 0.987 Hom.: 14159

Bravo AF: 0.973

Asia WGS AF: 0.994 AC: 3457 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.7
DANN	Benign	0.54
PhyloP100		0.24
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs820167; hg19: chr17-73720900;