rs2736428

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025257.3(SLC44A4):c.90-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,603,954 control chromosomes in the GnomAD database, including 84,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6476 hom., cov: 32)

Exomes 𝑓: 0.32 ( 78171 hom. )

Consequence

SLC44A4
NM_025257.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.36

Publications

75 publications found

Variant links:

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

SLC44A4 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_025257.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-31876147-C-T is Benign according to our data. Variant chr6-31876147-C-T is described in ClinVar as Benign. ClinVar VariationId is 1253945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC44A4	NM_025257.3	MANE Select	c.90-18G>A	intron	N/A	NP_079533.2	A0A140VJH4
SLC44A4	NM_001178044.2		c.90-18G>A	intron	N/A	NP_001171515.1	Q53GD3-4
SLC44A4	NM_001178045.2		c.-139-18G>A	intron	N/A	NP_001171516.1	A0A1U9X8K7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC44A4	ENST00000229729.11	TSL:1 MANE Select	c.90-18G>A	intron	N/A	ENSP00000229729.6	Q53GD3-1
SLC44A4	ENST00000414427.1	TSL:5	c.75-18G>A	intron	N/A	ENSP00000398901.1	H0Y5I3
SLC44A4	ENST00000882851.1		c.90-18G>A	intron	N/A	ENSP00000552910.1

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39589

AN:

151872

Hom.:

6474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0675

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.354

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.376

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.273

GnomAD2 exomes

AF:

0.335

AC:

81429

AN:

243248

AF XY:

0.338

show subpopulations

Gnomad AFR exome

AF:

0.0612

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.526

Gnomad EAS exome

AF:

0.355

Gnomad FIN exome

AF:

0.308

Gnomad NFE exome

AF:

0.348

Gnomad OTH exome

AF:

0.337

GnomAD4 exome

AF:

0.321

AC:

466695

AN:

1451964

Hom.:

78171

Cov.:

AF XY:

0.324

AC XY:

233999

AN XY:

721850

show subpopulations

African (AFR)

AF:

0.0569

AC:

1896

AN:

33342

American (AMR)

AF:

0.388

AC:

17093

AN:

44092

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

13143

AN:

25722

East Asian (EAS)

AF:

0.426

AC:

16850

AN:

39558

South Asian (SAS)

AF:

0.304

AC:

25907

AN:

85274

European-Finnish (FIN)

AF:

0.297

AC:

15746

AN:

52988

Middle Eastern (MID)

AF:

0.374

AC:

2139

AN:

5726

European-Non Finnish (NFE)

AF:

0.322

AC:

355540

AN:

1105236

Other (OTH)

AF:

0.306

AC:

18381

AN:

60026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

14640

29279

43919

58558

73198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11316

22632

33948

45264

56580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.261

AC:

39594

AN:

151990

Hom.:

6476

Cov.:

AF XY:

0.261

AC XY:

19421

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.0673

AC:

2792

AN:

41500

American (AMR)

AF:

0.323

AC:

4935

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1797

AN:

3470

East Asian (EAS)

AF:

0.354

AC:

1827

AN:

5156

South Asian (SAS)

AF:

0.306

AC:

1473

AN:

4812

European-Finnish (FIN)

AF:

0.300

AC:

3162

AN:

10534

Middle Eastern (MID)

AF:

0.387

AC:

113

AN:

292

European-Non Finnish (NFE)

AF:

0.332

AC:

22534

AN:

67940

Other (OTH)

AF:

0.272

AC:

574

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1383

2766

4149

5532

6915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.320

Hom.:

28136

Bravo

AF:

0.254

Asia WGS

AF:

0.273

AC:

953

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.0

(source)

DANN

Benign

0.86

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over