chr5-52944945-A-G

Variant names:

• chr5-52944945-A-G
• rs143105379
• NM_181501.2:c.3288A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_181501.2(ITGA1):​c.3288A>G​(p.Ser1096Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,607,492 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (14 hom.)
• Consequence: ITGA1 NM_181501.2 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.717
• Publications: 5 publications found

Genes affected

ITGA1 (HGNC:6134): (integrin subunit alpha 1) This gene encodes the alpha 1 subunit of integrin receptors. This protein heterodimerizes with the beta 1 subunit to form a cell-surface receptor for collagen and laminin. The heterodimeric receptor is involved in cell-cell adhesion and may play a role in inflammation and fibrosis. The alpha 1 subunit contains an inserted (I) von Willebrand factor type I domain which is thought to be involved in collagen binding. [provided by RefSeq, Jul 2008]

ITGA2-AS1 (HGNC:40306): (ITGA2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 5-52944945-A-G is Benign according to our data. Variant chr5-52944945-A-G is described in ClinVar as Benign. ClinVar VariationId is 725830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.717 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 14 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181501.2. 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
	ITGA1	NM_181501.2	MANE Select	c.3288A>G	p.Ser1096Ser	splice_region synonymous	Exon 27 of 29	NP_852478.1	P56199
	ITGA2-AS1	NR_186583.1		n.353+3880T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA1	ENST00000282588.7	TSL:1 MANE Select	c.3288A>G	p.Ser1096Ser	splice_region synonymous	Exon 27 of 29	ENSP00000282588.5	P56199
	ITGA1	ENST00000504669.5	TSL:1	n.5963A>G		splice_region non_coding_transcript_exon	Exon 16 of 18
	ITGA1	ENST00000506275.1	TSL:1	n.3169A>G		splice_region non_coding_transcript_exon	Exon 5 of 7

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 337 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00340

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00294 AC: 738 AN: 250638 AF XY: 0.00295

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00177

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00585

Gnomad NFE exome AF: 0.00449

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00369 AC: 5365 AN: 1455170 Hom.: 14 Cov.: 28 AF XY: 0.00362 AC XY: 2625 AN XY: 724500

African (AFR) AF: 0.000241 AC: 8 AN: 33218

American (AMR) AF: 0.00208 AC: 93 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.000349 AC: 30 AN: 86080

European-Finnish (FIN) AF: 0.00587 AC: 311 AN: 52976

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5752

European-Non Finnish (NFE) AF: 0.00432 AC: 4783 AN: 1106710

Other (OTH) AF: 0.00218 AC: 131 AN: 60138

GnomAD4 genome AF: 0.00221 AC: 337 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.00231 AC XY: 172 AN XY: 74472

African (AFR) AF: 0.000481 AC: 20 AN: 41582

American (AMR) AF: 0.00176 AC: 27 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00490 AC: 52 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00340 AC: 231 AN: 68026

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00286 Hom.: 0

Bravo AF: 0.00220

Asia WGS AF: 0.000578 AC: 2 AN: 3474

EpiCase AF: 0.00350

EpiControl AF: 0.00397

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	-0.47
CADD	Benign	3.7
DANN	Benign	0.75
PhyloP100		0.72
Mutation Taster		=96/4	polymorphism

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: rs143105379; hg19: chr5-52240775;