rs614549

Positions:

• chr6-31872848-A-G

Variant summary

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

The NM_025257.3(SLC44A4):​c.530-1287T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,544 control chromosomes in the GnomAD database, including 12,099 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 0.40 (12099 hom., cov: 32)
• Consequence: SLC44A4 NM_025257.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC44A4	NM_025257.3	c.530-1287T>C		intron_variant		ENST00000229729.11
SLC44A4	NM_001178044.2	c.404-1287T>C		intron_variant
SLC44A4	NM_001178045.2	c.302-1287T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A4	ENST00000229729.11	c.530-1287T>C		intron_variant		1	NM_025257.3	P1
SLC44A4	ENST00000375562.8	c.404-1287T>C		intron_variant		2
SLC44A4	ENST00000414427.1	c.517-1287T>C		intron_variant		5
SLC44A4	ENST00000544672.5	c.302-1287T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59884 AN: 151422 Hom.: 12090 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.396 AC: 59938 AN: 151544 Hom.: 12099 Cov.: 32 AF XY: 0.394 AC XY: 29181 AN XY: 74016

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.421

Alfa AF: 0.400 Hom.: 16279

Bravo AF: 0.408

Asia WGS AF: 0.360 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.6
DANN	Benign	0.82

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: rs614549; hg19: chr6-31840625;