rs9267658

chr6-31878208-T-Cchr6-31878208-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025257.3(SLC44A4):c.40+733A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,506 control chromosomes in the GnomAD database, including 63,915 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 0.91 (63597 hom., cov: 28)
  • Exomes 𝑓: 0.91 (318 hom.)
• Consequence: SLC44A4 NM_025257.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

Genes affected

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]

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

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 (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC44A4	NM_025257.3	c.40+733A>G		intron_variant		ENST00000229729.11
EHMT2-AS1	NR_174947.1	n.271+130T>C		intron_variant, non_coding_transcript_variant
SLC44A4	NM_001178044.2	c.40+733A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A4	ENST00000229729.11	c.40+733A>G		intron_variant		1	NM_025257.3	P1
EHMT2-AS1	ENST00000642849.1	n.271+130T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138588 AN: 151632 Hom.: 63533 Cov.: 28

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.940

GnomAD4 exome AF: 0.914 AC: 691 AN: 756 Hom.: 318 AF XY: 0.919 AC XY: 566 AN XY: 616

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.901

Gnomad4 OTH exome AF: 0.964

GnomAD4 genome AF: 0.914 AC: 138710 AN: 151750 Hom.: 63597 Cov.: 28 AF XY: 0.915 AC XY: 67862 AN XY: 74144

Gnomad4 AFR AF: 0.974

Gnomad4 AMR AF: 0.936

Gnomad4 ASJ AF: 0.968

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.974

Gnomad4 FIN AF: 0.874

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.941

Alfa AF: 0.885 Hom.: 94625

Bravo AF: 0.922

Asia WGS AF: 0.980 AC: 3410 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	11
Dann	Benign	0.87

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: rs9267658; hg19: chr6-31845985;