rs587777210

Variant names:

• chrX-71305086-C-G
• rs587777210
• NM_012278.4:c.938C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_012278.4(ITGB1BP2):​c.938C>G​(p.Ala313Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 1,209,399 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000053 (0 hom. 21 hem.)
• Consequence: ITGB1BP2 NM_012278.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.08
• Publications: 3 publications found

Genes affected

ITGB1BP2 (HGNC:6154): (integrin subunit beta 1 binding protein 2) This gene encodes a protein with two cysteine and histidine-rich (CHORD) domains, PXXP motifs, YXXI/P motifs, putative SH2 and SH3 domain binding motifs, and an acidic region at the C-terminus that can bind calcium. Two hybrid analysis showed that this protein interacts with the cytoplasmic domain of the beta 1 integrin subunit and is thought to act as a chaperone protein. Studies in the mouse ortholog of this gene indicate that absence of this gene in mouse results in failed cardiac hypertrophy in response to mechanical stress. Alternative splicing results in multiple transcript variants encoding different isoforms, including an isoform that lacks several domains, including one of the CHORD domains. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10649791).
• BS2: High Hemizygotes in GnomAdExome4 at 21 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012278.4. 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
	ITGB1BP2	NM_012278.4	MANE Select	c.938C>G	p.Ala313Gly	missense	Exon 11 of 11	NP_036410.1	Q9UKP3-1
	ITGB1BP2	NM_001303277.3		c.569C>G	p.Ala190Gly	missense	Exon 8 of 8	NP_001290206.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGB1BP2	ENST00000373829.8	TSL:1 MANE Select	c.938C>G	p.Ala313Gly	missense	Exon 11 of 11	ENSP00000362935.3	Q9UKP3-1
	ITGB1BP2	ENST00000538820.1	TSL:1	c.884C>G	p.Ala295Gly	missense	Exon 10 of 10	ENSP00000440289.1	Q9UKP3-2
	ITGB1BP2	ENST00000970300.1		c.875C>G	p.Ala292Gly	missense	Exon 10 of 10	ENSP00000640359.1

Frequencies

GnomAD3 genomes AF: 0.0000269 AC: 3 AN: 111699 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000564

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000439 AC: 8 AN: 182363 AF XY: 0.0000299

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000985

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000528 AC: 58 AN: 1097700 Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 21 AN XY: 363068

African (AFR) AF: 0.00 AC: 0 AN: 26395

American (AMR) AF: 0.00 AC: 0 AN: 35190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19372

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40521

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4081

European-Non Finnish (NFE) AF: 0.0000653 AC: 55 AN: 841806

Other (OTH) AF: 0.0000651 AC: 3 AN: 46074

GnomAD4 genome AF: 0.0000269 AC: 3 AN: 111699 Hom.: 0 Cov.: 23 AF XY: 0.0000295 AC XY: 1 AN XY: 33873

African (AFR) AF: 0.00 AC: 0 AN: 30738

American (AMR) AF: 0.00 AC: 0 AN: 10395

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.00 AC: 0 AN: 2680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000564 AC: 3 AN: 53157

Other (OTH) AF: 0.00 AC: 0 AN: 1500

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.024
Sift	Benign	0.13	T
Sift4G	Benign	0.25	T
Polyphen		0.016	B
Vest4		0.089
MVP		0.92
MPC		0.36
ClinPred		0.032	T
GERP RS		2.5
Varity_R		0.15
gMVP		0.16
Mutation Taster		=94/6	polymorphism

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: rs587777210; hg19: chrX-70524936;