10-32920338-G-T

Variant names:

• chr10-32920338-G-T
• rs2230396
• NM_002211.4:c.1176C>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002211.4(ITGB1):​c.1176C>A​(p.Gly392Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 1,611,972 control chromosomes in the GnomAD database, including 620,981 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G392G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.82 (52461 hom., cov: 32)
  • Exomes 𝑓: 0.88 (568520 hom.)
• Consequence: ITGB1 NM_002211.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 39 publications found

Genes affected

ITGB1 (HGNC:6153): (integrin subunit beta 1) Integrins are heterodimeric proteins made up of alpha and beta subunits. At least 18 alpha and 8 beta subunits have been described in mammals. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. This gene encodes a beta subunit. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.562 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002211.4. 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
	ITGB1	NM_002211.4	MANE Select	c.1176C>A	p.Gly392Gly	synonymous	Exon 10 of 16	NP_002202.2
	ITGB1	NM_033668.2		c.1176C>A	p.Gly392Gly	synonymous	Exon 9 of 16	NP_391988.1	P05556-5
	ITGB1	NM_133376.3		c.1176C>A	p.Gly392Gly	synonymous	Exon 10 of 16	NP_596867.1	P05556-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB1	ENST00000302278.8	TSL:1 MANE Select	c.1176C>A	p.Gly392Gly	synonymous	Exon 10 of 16	ENSP00000303351.3	P05556-1
	ITGB1	ENST00000488427.2	TSL:1	c.1005C>A	p.Gly335Gly	synonymous	Exon 10 of 16	ENSP00000417508.2	H7C4K3
	ITGB1	ENST00000966597.1		c.1176C>A	p.Gly392Gly	synonymous	Exon 10 of 17	ENSP00000636656.1

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125357 AN: 151984 Hom.: 52424 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.836

GnomAD2 exomes AF: 0.861 AC: 216033 AN: 251006 AF XY: 0.863

Gnomad AFR exome AF: 0.676

Gnomad AMR exome AF: 0.907

Gnomad ASJ exome AF: 0.905

Gnomad EAS exome AF: 0.679

Gnomad FIN exome AF: 0.875

Gnomad NFE exome AF: 0.892

Gnomad OTH exome AF: 0.872

GnomAD4 exome AF: 0.881 AC: 1286242 AN: 1459868 Hom.: 568520 Cov.: 37 AF XY: 0.881 AC XY: 639955 AN XY: 726420

African (AFR) AF: 0.665 AC: 22221 AN: 33396

American (AMR) AF: 0.903 AC: 40371 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 23658 AN: 26118

East Asian (EAS) AF: 0.689 AC: 27306 AN: 39614

South Asian (SAS) AF: 0.871 AC: 75060 AN: 86182

European-Finnish (FIN) AF: 0.875 AC: 46686 AN: 53376

Middle Eastern (MID) AF: 0.853 AC: 4914 AN: 5762

European-Non Finnish (NFE) AF: 0.895 AC: 993558 AN: 1110412

Other (OTH) AF: 0.870 AC: 52468 AN: 60320

GnomAD4 genome AF: 0.825 AC: 125446 AN: 152104 Hom.: 52461 Cov.: 32 AF XY: 0.824 AC XY: 61236 AN XY: 74358

African (AFR) AF: 0.678 AC: 28106 AN: 41452

American (AMR) AF: 0.873 AC: 13353 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3153 AN: 3470

East Asian (EAS) AF: 0.675 AC: 3479 AN: 5152

South Asian (SAS) AF: 0.865 AC: 4167 AN: 4820

European-Finnish (FIN) AF: 0.879 AC: 9291 AN: 10574

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 61000 AN: 68026

Other (OTH) AF: 0.838 AC: 1769 AN: 2110

Alfa AF: 0.869 Hom.: 98402

Bravo AF: 0.818

Asia WGS AF: 0.819 AC: 2849 AN: 3478

EpiCase AF: 0.894

EpiControl AF: 0.893

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.7
DANN	Benign	0.66
PhyloP100		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2230396; hg19: chr10-33209266; COSMIC: COSV56480050;