rs76424398

Variant names:

• chr3-37777549-G-A
• rs76424398
• NM_002207.3:c.2667+32G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-37777549-G-A
• chr3-37777549-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002207.3(ITGA9):​c.2667+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,612,482 control chromosomes in the GnomAD database, including 1,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (102 hom., cov: 33)
  • Exomes 𝑓: 0.039 (1232 hom.)
• Consequence: ITGA9 NM_002207.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.362
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-37777549-G-A is Benign according to our data. Variant chr3-37777549-G-A is described in ClinVar as Benign. ClinVar VariationId is 94048.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0312 (4749/152248) while in subpopulation NFE AF = 0.0479 (3256/68020). AF 95% confidence interval is 0.0465. There are 102 homozygotes in GnomAd4. There are 2252 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 102 gene

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.2667+32G>A		intron	N/A	NP_002198.2
	ITGA9-AS1	NR_110531.1		n.257-23497C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA9	ENST00000264741.10	TSL:1 MANE Select	c.2667+32G>A		intron	N/A	ENSP00000264741.5	Q13797
	ITGA9	ENST00000921363.1		c.2664+32G>A		intron	N/A	ENSP00000591422.1
	ITGA9	ENST00000944256.1		c.2664+32G>A		intron	N/A	ENSP00000614315.1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4747 AN: 152130 Hom.: 101 Cov.: 33

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0705

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.0366

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0479

Gnomad OTH AF: 0.0259

GnomAD2 exomes AF: 0.0311 AC: 7820 AN: 251212 AF XY: 0.0316

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.0161

Gnomad ASJ exome AF: 0.0216

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0370

Gnomad NFE exome AF: 0.0475

Gnomad OTH exome AF: 0.0335

GnomAD4 exome AF: 0.0386 AC: 56384 AN: 1460234 Hom.: 1232 Cov.: 31 AF XY: 0.0385 AC XY: 27993 AN XY: 726510

African (AFR) AF: 0.0107 AC: 358 AN: 33468

American (AMR) AF: 0.0169 AC: 756 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 542 AN: 26116

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39680

South Asian (SAS) AF: 0.0152 AC: 1307 AN: 86170

European-Finnish (FIN) AF: 0.0381 AC: 2033 AN: 53370

Middle Eastern (MID) AF: 0.0267 AC: 150 AN: 5622

European-Non Finnish (NFE) AF: 0.0443 AC: 49197 AN: 1110790

Other (OTH) AF: 0.0338 AC: 2039 AN: 60306

GnomAD4 genome AF: 0.0312 AC: 4749 AN: 152248 Hom.: 102 Cov.: 33 AF XY: 0.0303 AC XY: 2252 AN XY: 74446

African (AFR) AF: 0.0118 AC: 490 AN: 41546

American (AMR) AF: 0.0231 AC: 354 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4822

European-Finnish (FIN) AF: 0.0366 AC: 388 AN: 10594

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0479 AC: 3256 AN: 68020

Other (OTH) AF: 0.0256 AC: 54 AN: 2110

Alfa AF: 0.0419 Hom.: 238

Bravo AF: 0.0290

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	15
DANN	Benign	0.68
PhyloP100		0.36
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: rs76424398; hg19: chr3-37819040;