rs4947332

Variant names:

• chr6-31866420-C-T
• rs4947332
• NM_025257.3:c.1234-294G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 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=-0.88).
• 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 rank	MANE	Protein	UniProt
SLC44A4	NM_025257.3	c.1234-294G>A		intron_variant	Intron 13 of 20	ENST00000229729.11	NP_079533.2
SLC44A4	NM_001178044.2	c.1108-294G>A		intron_variant	Intron 12 of 19		NP_001171515.1
SLC44A4	NM_001178045.2	c.1006-294G>A		intron_variant	Intron 13 of 20		NP_001171516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A4	ENST00000229729.11	c.1234-294G>A		intron_variant	Intron 13 of 20	1	NM_025257.3	ENSP00000229729.6
SLC44A4	ENST00000414427.1	c.883-294G>A		intron_variant	Intron 11 of 12	5		ENSP00000398901.1

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

African (AFR) AF: 0.0890 AC: 3691 AN: 41492

American (AMR) AF: 0.0320 AC: 489 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.0141 AC: 73 AN: 5186

South Asian (SAS) AF: 0.0396 AC: 191 AN: 4820

European-Finnish (FIN) AF: 0.0157 AC: 166 AN: 10602

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0272 AC: 1847 AN: 68012

Other (OTH) AF: 0.0403 AC: 85 AN: 2108

Alfa AF: 0.0317 Hom.: 407

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
PhyloP100		-0.37
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: rs4947332; hg19: chr6-31834197;