rs4241261

Variant names:

• chr2-69836528-A-G
• rs4241261
• NM_178439.5:c.261-1019A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-69836528-A-G
• chr2-69836528-A-T

Variant summary

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

The NM_178439.5(GMCL1):​c.261-1019A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,050 control chromosomes in the GnomAD database, including 29,714 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 0.60 (29714 hom., cov: 32)
• Consequence: GMCL1 NM_178439.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 9 publications found

Genes affected

GMCL1 (HGNC:23843): (germ cell-less 1, spermatogenesis associated) This gene encodes a nuclear envelope protein that appears to be involved in spermatogenesis, either directly or by influencing genes that play a more direct role in the process. This multi-exon locus is the homolog of the mouse and drosophila germ cell-less gene but the human genome also contains a single-exon locus on chromosome 5 that contains an open reading frame capable of encoding a highly-related protein. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMCL1	NM_178439.5	c.261-1019A>G		intron_variant	Intron 1 of 13	ENST00000282570.4	NP_848526.1
GMCL1	XM_011533033.3	c.261-1019A>G		intron_variant	Intron 1 of 12		XP_011531335.1
GMCL1	XR_007079574.1	n.494-1019A>G		intron_variant	Intron 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMCL1	ENST00000282570.4	c.261-1019A>G		intron_variant	Intron 1 of 13	1	NM_178439.5	ENSP00000282570.3
GMCL1	ENST00000468386.2	n.468-1019A>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90757 AN: 151932 Hom.: 29647 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.598 AC: 90881 AN: 152050 Hom.: 29714 Cov.: 32 AF XY: 0.599 AC XY: 44514 AN XY: 74300

African (AFR) AF: 0.866 AC: 35954 AN: 41524

American (AMR) AF: 0.647 AC: 9874 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3468

East Asian (EAS) AF: 0.673 AC: 3483 AN: 5174

South Asian (SAS) AF: 0.434 AC: 2089 AN: 4818

European-Finnish (FIN) AF: 0.528 AC: 5565 AN: 10534

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30751 AN: 67954

Other (OTH) AF: 0.544 AC: 1146 AN: 2108

Alfa AF: 0.537 Hom.: 6547

Bravo AF: 0.623

Asia WGS AF: 0.575 AC: 1999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.7
DANN	Benign	0.57
PhyloP100		0.066
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4241261; hg19: chr2-70063660;