2-160107548-A-G

Variant names:

• chr2-160107548-A-G
• rs13008664
• NM_000888.5:c.2268+131T>C

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+131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 758,344 control chromosomes in the GnomAD database, including 74,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11722 hom., cov: 31)
  • Exomes 𝑓: 0.44 (62386 hom.)
• Consequence: ITGB6 NM_000888.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.440
• Publications: 0 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=-0.88).
• BP6: Variant 2-160107548-A-G is Benign according to our data. Variant chr2-160107548-A-G is described in ClinVar as Benign. ClinVar VariationId is 1269204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 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+131T>C		intron	N/A	NP_000879.2
	ITGB6	NM_001282353.2		c.2268+131T>C		intron	N/A	NP_001269282.1	P18564-1
	ITGB6	NM_001282388.2		c.2142+131T>C		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+131T>C		intron	N/A	ENSP00000283249.2	P18564-1
	ITGB6	ENST00000409872.1	TSL:1	c.2268+131T>C		intron	N/A	ENSP00000386367.1	P18564-1
	ITGB6	ENST00000958494.1		c.2355+131T>C		intron	N/A	ENSP00000628553.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54825 AN: 151592 Hom.: 11721 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.442 AC: 267925 AN: 606630 Hom.: 62386 AF XY: 0.437 AC XY: 139139 AN XY: 318586

African (AFR) AF: 0.131 AC: 2093 AN: 15972

American (AMR) AF: 0.318 AC: 8893 AN: 27986

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 4799 AN: 15020

East Asian (EAS) AF: 0.341 AC: 12019 AN: 35234

South Asian (SAS) AF: 0.283 AC: 14513 AN: 51318

European-Finnish (FIN) AF: 0.505 AC: 19499 AN: 38598

Middle Eastern (MID) AF: 0.278 AC: 1045 AN: 3758

European-Non Finnish (NFE) AF: 0.495 AC: 191994 AN: 387670

Other (OTH) AF: 0.421 AC: 13070 AN: 31074

GnomAD4 genome AF: 0.361 AC: 54833 AN: 151714 Hom.: 11722 Cov.: 31 AF XY: 0.363 AC XY: 26926 AN XY: 74102

African (AFR) AF: 0.136 AC: 5658 AN: 41456

American (AMR) AF: 0.359 AC: 5475 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1101 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1574 AN: 5146

South Asian (SAS) AF: 0.280 AC: 1346 AN: 4810

European-Finnish (FIN) AF: 0.519 AC: 5422 AN: 10456

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.487 AC: 33058 AN: 67812

Other (OTH) AF: 0.345 AC: 726 AN: 2102

Alfa AF: 0.303 Hom.: 2024

Bravo AF: 0.341

Asia WGS AF: 0.337 AC: 1170 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	-0.88
CADD	Benign	5.6
DANN	Benign	0.19
PhyloP100		0.44
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: rs13008664; hg19: chr2-160964059;