NM_000888.5:c.2269-115T>A

Variant names:

• chr2-160101949-A-T
• rs4078235
• NM_000888.5:c.2269-115T>A

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.2269-115T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 638,084 control chromosomes in the GnomAD database, including 8,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2607 hom., cov: 33)
  • Exomes 𝑓: 0.15 (6371 hom.)
• Consequence: ITGB6 NM_000888.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.200
• Publications: 3 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=-0.85).
• BP6: Variant 2-160101949-A-T is Benign according to our data. Variant chr2-160101949-A-T is described in ClinVar as Benign. ClinVar VariationId is 1221702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.3 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.2269-115T>A		intron	N/A	NP_000879.2
	ITGB6	NM_001282353.2		c.2269-115T>A		intron	N/A	NP_001269282.1	P18564-1
	ITGB6	NM_001282388.2		c.2143-115T>A		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.2269-115T>A		intron	N/A	ENSP00000283249.2	P18564-1
	ITGB6	ENST00000409872.1	TSL:1	c.2269-115T>A		intron	N/A	ENSP00000386367.1	P18564-1
	ITGB6	ENST00000958494.1		c.2356-115T>A		intron	N/A	ENSP00000628553.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26434 AN: 152020 Hom.: 2589 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.188

GnomAD4 exome AF: 0.152 AC: 73941 AN: 485950 Hom.: 6371 AF XY: 0.149 AC XY: 38899 AN XY: 261216

African (AFR) AF: 0.196 AC: 2401 AN: 12238

American (AMR) AF: 0.375 AC: 6675 AN: 17788

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 2220 AN: 15584

East Asian (EAS) AF: 0.163 AC: 4981 AN: 30582

South Asian (SAS) AF: 0.118 AC: 5590 AN: 47298

European-Finnish (FIN) AF: 0.110 AC: 4126 AN: 37612

Middle Eastern (MID) AF: 0.153 AC: 545 AN: 3554

European-Non Finnish (NFE) AF: 0.146 AC: 42951 AN: 294144

Other (OTH) AF: 0.164 AC: 4452 AN: 27150

GnomAD4 genome AF: 0.174 AC: 26483 AN: 152134 Hom.: 2607 Cov.: 33 AF XY: 0.173 AC XY: 12874 AN XY: 74380

African (AFR) AF: 0.196 AC: 8129 AN: 41500

American (AMR) AF: 0.307 AC: 4693 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.165 AC: 854 AN: 5174

South Asian (SAS) AF: 0.127 AC: 615 AN: 4824

European-Finnish (FIN) AF: 0.0975 AC: 1035 AN: 10610

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.149 AC: 10151 AN: 67966

Other (OTH) AF: 0.187 AC: 395 AN: 2112

Alfa AF: 0.161 Hom.: 265

Bravo AF: 0.194

Asia WGS AF: 0.155 AC: 540 AN: 3476

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	-0.85
CADD	Benign	2.7
DANN	Benign	0.43
PhyloP100		-0.20
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: rs4078235; hg19: chr2-160958460;