2-9405901-C-T

Variant names:

• chr2-9405901-C-T
• rs10593
• NM_004763.5:c.*933G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004763.5(ITGB1BP1):​c.*933G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,194 control chromosomes in the GnomAD database, including 50,607 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.

• Frequency:
  • Genomes: 𝑓 0.81 (50606 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: ITGB1BP1 NM_004763.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 8 publications found

Genes affected

ITGB1BP1 (HGNC:23927): (integrin subunit beta 1 binding protein 1) The cytoplasmic domains of integrins are essential for cell adhesion. The protein encoded by this gene binds to the beta1 integrin cytoplasmic domain. The interaction between this protein and beta1 integrin is highly specific. Two isoforms of this protein are derived from alternatively spliced transcripts. The shorter form of this protein does not interact with the beta1 integrin cytoplasmic domain. The longer form is a phosphoprotein and the extent of its phosphorylation is regulated by the cell-matrix interaction, suggesting an important role of this protein during integrin-dependent cell adhesion. Several transcript variants, some protein-coding and some non-protein coding, have been found for this gene. [provided by RefSeq, Jan 2016]

ASAP2 (HGNC:2721): (ArfGAP with SH3 domain, ankyrin repeat and PH domain 2) This gene encodes a multidomain protein containing an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology (PH) domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal Src homology 3 (SH3) domain. The protein localizes in the Golgi apparatus and at the plasma membrane, where it colocalizes with protein tyrosine kinase 2-beta (PYK2). The encoded protein forms a stable complex with PYK2 in vivo. This interaction appears to be mediated by binding of its SH3 domain to the C-terminal proline-rich domain of PYK2. The encoded protein is tyrosine phosphorylated by activated PYK2. It has catalytic activity for class I and II ArfGAPs in vitro, and can bind the class III Arf ARF6 without immediate GAP activity. The encoded protein is believed to function as an ARF GAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. In addition, it functions as a substrate and downstream target for PYK2 and SRC, a pathway that may be involved in the regulation of vesicular transport. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGB1BP1	NM_004763.5	c.*933G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000355346.9	NP_004754.1
ASAP2	NM_003887.3	c.*2574C>T		downstream_gene_variant		ENST00000281419.8	NP_003878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB1BP1	ENST00000355346.9	c.*933G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_004763.5	ENSP00000347504.4
ASAP2	ENST00000281419.8	c.*2574C>T		downstream_gene_variant		1	NM_003887.3	ENSP00000281419.3

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122976 AN: 152064 Hom.: 50588 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.820

GnomAD4 exome AF: 0.500 AC: 6 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 5 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.375 AC: 3 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.809 AC: 123042 AN: 152182 Hom.: 50606 Cov.: 32 AF XY: 0.812 AC XY: 60392 AN XY: 74388

African (AFR) AF: 0.643 AC: 26701 AN: 41496

American (AMR) AF: 0.866 AC: 13252 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2949 AN: 3472

East Asian (EAS) AF: 0.852 AC: 4402 AN: 5164

South Asian (SAS) AF: 0.797 AC: 3846 AN: 4824

European-Finnish (FIN) AF: 0.924 AC: 9805 AN: 10610

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.872 AC: 59278 AN: 68004

Other (OTH) AF: 0.815 AC: 1722 AN: 2112

Alfa AF: 0.854 Hom.: 90903

Bravo AF: 0.797

Asia WGS AF: 0.787 AC: 2733 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.55
PhyloP100		0.097
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: rs10593; hg19: chr2-9546030;