Variant chr1-108885627-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013296.5(GPSM2):c.56+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,124,092 control chromosomes in the GnomAD database, including 49,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 10032 hom., cov: 32)

Exomes 𝑓: 0.27 ( 39146 hom. )

Consequence

GPSM2
NM_013296.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.851

Variant links:

Genes affected

GPSM2 (HGNC:29501): (G protein signaling modulator 2) The protein encoded by this gene belongs to a family of proteins that modulate activation of G proteins, which transduce extracellular signals received by cell surface receptors into integrated cellular responses. The N-terminal half of this protein contains 10 copies of leu-gly-asn (LGN) repeat, and the C-terminal half contains 4 GoLoco motifs, which are involved in guanine nucleotide exchange. This protein may play a role in neuroblast division and in the development of normal hearing. Mutations in this gene are associated with autosomal recessive nonsyndromic deafness (DFNB82). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

GPSM2 links:

AKNAD1 (HGNC:28398): (AKNA domain containing 1) This gene encodes a protein which contains a domain found in an AT-hook-containing transcription factor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

AKNAD1 links:

CLCC1 (HGNC:29675): (chloride channel CLIC like 1) Predicted to enable chloride channel activity. Predicted to be involved in chloride transport. Located in endoplasmic reticulum and mitochondria-associated endoplasmic reticulum membrane. Implicated in retinitis pigmentosa 32. [provided by Alliance of Genome Resources, Apr 2022]

CLCC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-108885627-G-A is Benign according to our data. Variant chr1-108885627-G-A is described in ClinVar as [Benign]. Clinvar id is 1269298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPSM2	NM_013296.5 linkuse as main transcript	c.56+49G>A		intron_variant		ENST00000264126.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPSM2	ENST00000264126.9 linkuse as main transcript	c.56+49G>A		intron_variant		1	NM_013296.5	P1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51811

AN:

151844

Hom.:

10000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.0531

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.308

GnomAD3 exomes

AF:

0.275

AC:

67768

AN:

246266

Hom.:

10455

AF XY:

0.273

AC XY:

36455

AN XY:

133330

show subpopulations

Gnomad AFR exome

AF:

0.526

Gnomad AMR exome

AF:

0.222

Gnomad ASJ exome

AF:

0.329

Gnomad EAS exome

AF:

0.0585

Gnomad SAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.279

GnomAD4 exome

AF:

0.273

AC:

265508

AN:

972130

Hom.:

39146

Cov.:

AF XY:

0.274

AC XY:

138081

AN XY:

504496

show subpopulations

Gnomad4 AFR exome

AF:

0.525

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.330

Gnomad4 EAS exome

AF:

0.0600

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.276

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.342

AC:

51896

AN:

151962

Hom.:

10032

Cov.:

AF XY:

0.337

AC XY:

25008

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.334

Gnomad4 EAS

AF:

0.0531

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.287

Gnomad4 OTH

AF:

0.308

Alfa

AF:

0.303

Hom.:

2725

Bravo

AF:

0.343

Asia WGS

AF:

0.202

AC:

701

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over