rs605203

Variant names:

• chr6-31879235-C-A
• rs605203
• ENST00000642849.1:n.272-1009C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31879235-C-A
• chr6-31879235-C-G
• chr6-31879235-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_174947.1(EHMT2-AS1):​n.272-1009C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,126 control chromosomes in the GnomAD database, including 45,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.77 (45918 hom., cov: 31)
• Consequence: EHMT2-AS1 NR_174947.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69
• Publications: 41 publications found

Genes affected

EHMT2-AS1 (HGNC:39751): (EHMT2 and SLC44A4 antisense RNA 1)

SLC44A4 (HGNC:13941): (solute carrier family 44 member 4) The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC44A4 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal dominant 72

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-31879235-C-A is Benign according to our data. Variant chr6-31879235-C-A is described in ClinVar as Benign. ClinVar VariationId is 1283725.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_174947.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT2-AS1	NR_174947.1		n.272-1009C>A		intron	N/A
	SLC44A4	NM_025257.3	MANE Select	c.-255G>T		upstream_gene	N/A	NP_079533.2	A0A140VJH4
	SLC44A4	NM_001178044.2		c.-255G>T		upstream_gene	N/A	NP_001171515.1	Q53GD3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT2-AS1	ENST00000642849.1		n.272-1009C>A		intron	N/A
	SLC44A4	ENST00000229729.11	TSL:1 MANE Select	c.-255G>T		upstream_gene	N/A	ENSP00000229729.6	Q53GD3-1
	SLC44A4	ENST00000882851.1		c.-255G>T		upstream_gene	N/A	ENSP00000552910.1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116911 AN: 152008 Hom.: 45852 Cov.: 31

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.769 AC: 117038 AN: 152126 Hom.: 45918 Cov.: 31 AF XY: 0.773 AC XY: 57495 AN XY: 74366

African (AFR) AF: 0.889 AC: 36912 AN: 41498

American (AMR) AF: 0.869 AC: 13301 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2980 AN: 3468

East Asian (EAS) AF: 0.800 AC: 4144 AN: 5178

South Asian (SAS) AF: 0.878 AC: 4232 AN: 4822

European-Finnish (FIN) AF: 0.664 AC: 7025 AN: 10572

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45807 AN: 67962

Other (OTH) AF: 0.827 AC: 1746 AN: 2112

Alfa AF: 0.736 Hom.: 104909

Bravo AF: 0.790

Asia WGS AF: 0.886 AC: 3082 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.011
DANN	Benign	0.49
PhyloP100		-1.7
PromoterAI		0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs605203; hg19: chr6-31847012;