chr7-31578000-G-A

Variant names:

• chr7-31578000-G-A
• rs376757677
• NM_001257967.3:c.736G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001257967.3(ITPRID1):​c.736G>A​(p.Ala246Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,613,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: ITPRID1 NM_001257967.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00700

Genes affected

ITPRID1 (HGNC:27363): (ITPR interacting domain containing 1) Predicted to enable signaling receptor binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039349258).
• BP6: Variant 7-31578000-G-A is Benign according to our data. Variant chr7-31578000-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3111854.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRID1	NM_001257967.3	c.736G>A	p.Ala246Thr	missense_variant	Exon 9 of 15	ENST00000615280.5	NP_001244896.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPRID1	ENST00000615280.5	c.736G>A	p.Ala246Thr	missense_variant	Exon 9 of 15	2	NM_001257967.3	ENSP00000478518.2
ITPRID1	ENST00000407970.7	c.736G>A	p.Ala246Thr	missense_variant	Exon 8 of 14	1		ENSP00000384416.3
ITPRID1	ENST00000409210.1	c.460G>A	p.Ala154Thr	missense_variant	Exon 6 of 13	2		ENSP00000387214.1
ITPRID1	ENST00000319386.7	c.726+10G>A		intron_variant	Intron 8 of 13	2		ENSP00000313062.3

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000520 AC: 13 AN: 250154 Hom.: 0 AF XY: 0.0000444 AC XY: 6 AN XY: 135128

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000534 AC: 78 AN: 1461524 Hom.: 0 Cov.: 30 AF XY: 0.0000468 AC XY: 34 AN XY: 727022

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000621

Gnomad4 OTH exome AF: 0.0000663

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74292

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000774 Hom.: 0

Bravo AF: 0.0000831

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 21, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.65
DEOGEN2	Benign	0.0012	.;T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.25	T;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.039	T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.46	.;N;N;N
REVEL	Benign	0.015
Sift	Benign	0.44	.;T;T;T
Sift4G	Benign	0.65	T;T;T;T
Polyphen		0.014	.;B;.;.
Vest4		0.012
MVP		0.20
MPC		0.031
ClinPred		0.0047	T
GERP RS		-0.28
Varity_R		0.019
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs376757677; hg19: chr7-31617614; COSMIC: COSV60074122; COSMIC: COSV60074122;