rs7542414

Variant names:

• chr1-108883666-G-A
• rs7542414
• NM_013296.5:c.-248-1609G>A

Variant summary

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

The NM_013296.5(GPSM2):​c.-248-1609G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,984 control chromosomes in the GnomAD database, including 7,955 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 0.31 (7955 hom., cov: 32)
• Consequence: GPSM2 NM_013296.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 3 publications found

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]

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPSM2	NM_013296.5	c.-248-1609G>A		intron_variant	Intron 1 of 14	ENST00000264126.9	NP_037428.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPSM2	ENST00000264126.9	c.-248-1609G>A		intron_variant	Intron 1 of 14	1	NM_013296.5	ENSP00000264126.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47504 AN: 151866 Hom.: 7931 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.289

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.313 AC: 47576 AN: 151984 Hom.: 7955 Cov.: 32 AF XY: 0.310 AC XY: 23004 AN XY: 74302

African (AFR) AF: 0.427 AC: 17693 AN: 41438

American (AMR) AF: 0.231 AC: 3531 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3468

East Asian (EAS) AF: 0.0533 AC: 276 AN: 5180

South Asian (SAS) AF: 0.250 AC: 1207 AN: 4824

European-Finnish (FIN) AF: 0.305 AC: 3224 AN: 10556

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19474 AN: 67942

Other (OTH) AF: 0.289 AC: 610 AN: 2110

Alfa AF: 0.293 Hom.: 8601

Bravo AF: 0.311

Asia WGS AF: 0.198 AC: 689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.56
DANN	Benign	0.24
PhyloP100		-0.019
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7542414; hg19: chr1-109426288;