NM_002207.3:c.2234+7G>C

Variant names:

• chr3-37736990-G-C
• rs1118148
• NM_002207.3:c.2234+7G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002207.3(ITGA9):​c.2234+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,585,262 control chromosomes in the GnomAD database, including 57,836 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.34 (11086 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46750 hom.)
• Consequence: ITGA9 NM_002207.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002006
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.681
• Publications: 7 publications found

Genes affected

ITGA9 (HGNC:6145): (integrin subunit alpha 9) This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane glycoproteins composed of an alpha chain and a beta chain that mediate cell-cell and cell-matrix adhesion. The protein encoded by this gene, when bound to the beta 1 chain, forms an integrin that is a receptor for VCAM1, cytotactin and osteopontin. Expression of this gene has been found to be upregulated in small cell lung cancers. [provided by RefSeq, Jul 2008]

ITGA9-AS1 (HGNC:49668): (ITGA9 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-37736990-G-C is Benign according to our data. Variant chr3-37736990-G-C is described in ClinVar as Benign. ClinVar VariationId is 3060254.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002207.3. 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
	ITGA9	NM_002207.3	MANE Select	c.2234+7G>C		splice_region intron	N/A	NP_002198.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA9	ENST00000264741.10	TSL:1 MANE Select	c.2234+7G>C		splice_region intron	N/A	ENSP00000264741.5	Q13797
	ITGA9	ENST00000921363.1		c.2234+7G>C		splice_region intron	N/A	ENSP00000591422.1
	ITGA9	ENST00000944256.1		c.2231+7G>C		splice_region intron	N/A	ENSP00000614315.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52090 AN: 151954 Hom.: 11052 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.322

GnomAD2 exomes AF: 0.252 AC: 63251 AN: 251080 AF XY: 0.249

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.180

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.248

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.245 AC: 351549 AN: 1433190 Hom.: 46750 Cov.: 27 AF XY: 0.246 AC XY: 176030 AN XY: 715002

African (AFR) AF: 0.619 AC: 20096 AN: 32490

American (AMR) AF: 0.164 AC: 7319 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 7081 AN: 25962

East Asian (EAS) AF: 0.173 AC: 6851 AN: 39584

South Asian (SAS) AF: 0.256 AC: 21887 AN: 85616

European-Finnish (FIN) AF: 0.202 AC: 10785 AN: 53384

Middle Eastern (MID) AF: 0.303 AC: 1734 AN: 5718

European-Non Finnish (NFE) AF: 0.239 AC: 260145 AN: 1086298

Other (OTH) AF: 0.263 AC: 15651 AN: 59460

GnomAD4 genome AF: 0.343 AC: 52180 AN: 152072 Hom.: 11086 Cov.: 32 AF XY: 0.336 AC XY: 25010 AN XY: 74334

African (AFR) AF: 0.608 AC: 25202 AN: 41448

American (AMR) AF: 0.241 AC: 3676 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 953 AN: 3472

East Asian (EAS) AF: 0.181 AC: 935 AN: 5176

South Asian (SAS) AF: 0.256 AC: 1234 AN: 4818

European-Finnish (FIN) AF: 0.193 AC: 2038 AN: 10576

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.250 AC: 16982 AN: 67986

Other (OTH) AF: 0.322 AC: 680 AN: 2112

Alfa AF: 0.225 Hom.: 1259

Bravo AF: 0.359

EpiCase AF: 0.256

EpiControl AF: 0.254

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ITGA9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0
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: rs1118148; hg19: chr3-37778481; COSMIC: COSV53250065; COSMIC: COSV53250065;