6-31878208-T-C

Variant names:

• chr6-31878208-T-C
• rs9267658
• NM_025257.3:c.40+733A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 41 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025257.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A4	NM_025257.3	MANE Select	c.40+733A>G		intron	N/A	NP_079533.2
	SLC44A4	NM_001178044.2		c.40+733A>G		intron	N/A	NP_001171515.1
	EHMT2-AS1	NR_174947.1		n.271+130T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC44A4	ENST00000229729.11	TSL:1 MANE Select	c.40+733A>G		intron	N/A	ENSP00000229729.6
	SLC44A4	ENST00000414427.1	TSL:5	c.25+733A>G		intron	N/A	ENSP00000398901.1
	SLC44A4	ENST00000375562.8	TSL:2	c.40+733A>G		intron	N/A	ENSP00000364712.4

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

African (AFR) AF: 1.00 AC: 10 AN: 10

American (AMR) AF: 1.00 AC: 6 AN: 6

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 8 AN: 8

East Asian (EAS) AF: 1.00 AC: 26 AN: 26

South Asian (SAS) AF: 1.00 AC: 14 AN: 14

European-Finnish (FIN) AF: 1.00 AC: 6 AN: 6

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.901 AC: 564 AN: 626

Other (OTH) AF: 0.964 AC: 54 AN: 56

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

African (AFR) AF: 0.974 AC: 40304 AN: 41366

American (AMR) AF: 0.936 AC: 14279 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3358 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5101 AN: 5124

South Asian (SAS) AF: 0.974 AC: 4677 AN: 4802

European-Finnish (FIN) AF: 0.874 AC: 9242 AN: 10572

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58635 AN: 67848

Other (OTH) AF: 0.941 AC: 1982 AN: 2106

Alfa AF: 0.888 Hom.: 202489

Bravo AF: 0.922

Asia WGS AF: 0.980 AC: 3410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		0.088
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: rs9267658; hg19: chr6-31845985;