rs614549

Variant names:

• chr6-31872848-A-G
• rs614549
• NM_025257.3:c.530-1287T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 37 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]

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 -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 rank	MANE	Protein	UniProt
SLC44A4	NM_025257.3	c.530-1287T>C		intron_variant	Intron 7 of 20	ENST00000229729.11	NP_079533.2
SLC44A4	NM_001178044.2	c.404-1287T>C		intron_variant	Intron 6 of 19		NP_001171515.1
SLC44A4	NM_001178045.2	c.302-1287T>C		intron_variant	Intron 7 of 20		NP_001171516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A4	ENST00000229729.11	c.530-1287T>C		intron_variant	Intron 7 of 20	1	NM_025257.3	ENSP00000229729.6
SLC44A4	ENST00000414427.1	c.515-1287T>C		intron_variant	Intron 7 of 12	5		ENSP00000398901.1
SLC44A4	ENST00000375562.8	c.404-1287T>C		intron_variant	Intron 6 of 19	2		ENSP00000364712.4
SLC44A4	ENST00000544672.5	c.302-1287T>C		intron_variant	Intron 7 of 20	2		ENSP00000444109.1

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

African (AFR) AF: 0.435 AC: 17972 AN: 41290

American (AMR) AF: 0.443 AC: 6758 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 1999 AN: 3464

East Asian (EAS) AF: 0.399 AC: 2048 AN: 5130

South Asian (SAS) AF: 0.371 AC: 1783 AN: 4804

European-Finnish (FIN) AF: 0.304 AC: 3170 AN: 10436

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24783 AN: 67890

Other (OTH) AF: 0.421 AC: 881 AN: 2094

Alfa AF: 0.387 Hom.: 42750

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
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs614549; hg19: chr6-31840625;