rs4241261

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GMCL1	NM_178439.5	c.261-1019A>G		intron_variant		ENST00000282570.4
GMCL1	XM_011533033.3	c.261-1019A>G		intron_variant
GMCL1	XR_007079574.1	n.494-1019A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMCL1	ENST00000282570.4	c.261-1019A>G		intron_variant		1	NM_178439.5	P1
GMCL1	ENST00000468386.2	n.468-1019A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.544

Alfa AF: 0.559 Hom.: 4028

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4241261; hg19: chr2-70063660;