rs4947332

chr6-31866420-C-T

Variant summary

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

The NM_025257.3(SLC44A4):c.1234-294G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 152,186 control chromosomes in the GnomAD database, including 213 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 0.043 (213 hom., cov: 32)
• Consequence: SLC44A4 NM_025257.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC44A4	NM_025257.3	c.1234-294G>A		intron_variant		ENST00000229729.11
SLC44A4	NM_001178044.2	c.1108-294G>A		intron_variant
SLC44A4	NM_001178045.2	c.1006-294G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A4	ENST00000229729.11	c.1234-294G>A		intron_variant		1	NM_025257.3	P1

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6596 AN: 152068 Hom.: 214 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0407

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

GnomAD4 genome AF: 0.0433 AC: 6597 AN: 152186 Hom.: 213 Cov.: 32 AF XY: 0.0432 AC XY: 3217 AN XY: 74412

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.0320

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.0141

Gnomad4 SAS AF: 0.0396

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.0272

Gnomad4 OTH AF: 0.0403

Alfa AF: 0.0289 Hom.: 123

Bravo AF: 0.0462

Asia WGS AF: 0.0370 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.1
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4947332; hg19: chr6-31834197;