2-160107589-C-A

Variant names:

• chr2-160107589-C-A
• rs6724949
• NM_000888.5:c.2268+90G>T

Variant summary

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

The NM_000888.5(ITGB6):​c.2268+90G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00957 in 1,172,306 control chromosomes in the GnomAD database, including 535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (298 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (237 hom.)
• Consequence: ITGB6 NM_000888.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.29
• Publications: 1 publications found

Genes affected

ITGB6 (HGNC:6161): (integrin subunit beta 6) This gene encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors that function in signaling from the extracellular matrix to the cell. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. The encoded protein forms a dimer with an alpha v chain and this heterodimer can bind to ligands like fibronectin and transforming growth factor beta 1. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ITGB6 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta type 1H

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• amelogenesis imperfecta type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• amelogenesis imperfecta, type 3A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-160107589-C-A is Benign according to our data. Variant chr2-160107589-C-A is described in ClinVar as Benign. ClinVar VariationId is 1252601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000888.5. 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
	ITGB6	NM_000888.5	MANE Select	c.2268+90G>T		intron	N/A	NP_000879.2
	ITGB6	NM_001282353.2		c.2268+90G>T		intron	N/A	NP_001269282.1	P18564-1
	ITGB6	NM_001282388.2		c.2142+90G>T		intron	N/A	NP_001269317.1	E9PEE8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB6	ENST00000283249.7	TSL:1 MANE Select	c.2268+90G>T		intron	N/A	ENSP00000283249.2	P18564-1
	ITGB6	ENST00000409872.1	TSL:1	c.2268+90G>T		intron	N/A	ENSP00000386367.1	P18564-1
	ITGB6	ENST00000958494.1		c.2355+90G>T		intron	N/A	ENSP00000628553.1

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5658 AN: 152108 Hom.: 294 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.0283

GnomAD4 exome AF: 0.00543 AC: 5543 AN: 1020078 Hom.: 237 AF XY: 0.00490 AC XY: 2539 AN XY: 518230

African (AFR) AF: 0.126 AC: 2970 AN: 23516

American (AMR) AF: 0.0102 AC: 335 AN: 32938

Ashkenazi Jewish (ASJ) AF: 0.0500 AC: 964 AN: 19284

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37428

South Asian (SAS) AF: 0.000336 AC: 22 AN: 65446

European-Finnish (FIN) AF: 0.0000822 AC: 4 AN: 48642

Middle Eastern (MID) AF: 0.00770 AC: 36 AN: 4674

European-Non Finnish (NFE) AF: 0.000757 AC: 563 AN: 743448

Other (OTH) AF: 0.0145 AC: 648 AN: 44702

GnomAD4 genome AF: 0.0373 AC: 5681 AN: 152228 Hom.: 298 Cov.: 32 AF XY: 0.0353 AC XY: 2630 AN XY: 74444

African (AFR) AF: 0.123 AC: 5118 AN: 41512

American (AMR) AF: 0.0181 AC: 276 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00123 AC: 84 AN: 68018

Other (OTH) AF: 0.0280 AC: 59 AN: 2110

Alfa AF: 0.0152 Hom.: 158

Bravo AF: 0.0438

Asia WGS AF: 0.00953 AC: 33 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	-0.81
CADD	Benign	3.9
DANN	Benign	0.65
PhyloP100		1.3
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: rs6724949; hg19: chr2-160964100; COSMIC: COSV51794002;