dbSNP rs11966200: SLC44A4:c.1131-32G>A (chr6-31869289-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_025257.3(SLC44A4):c.1131-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,542,596 control chromosomes in the GnomAD database, including 862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.044 ( 212 hom., cov: 33)

Exomes 𝑓: 0.025 ( 650 hom. )

Consequence

SLC44A4
NM_025257.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36

Publications

27 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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-31869289-C-T is Benign according to our data. Variant chr6-31869289-C-T is described in ClinVar as Benign. ClinVar VariationId is 1249229.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SLC44A4	NM_025257.3 link	c.1131-32G>A	intron_variant	Intron 12 of 20	ENST00000229729.11	NP_079533.2
SLC44A4	NM_001178044.2 link	c.1005-32G>A	intron_variant	Intron 11 of 19		NP_001171515.1
SLC44A4	NM_001178045.2 link	c.903-32G>A	intron_variant	Intron 12 of 20		NP_001171516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A4	ENST00000229729.11 link	c.1131-32G>A		intron_variant	Intron 12 of 20	1	NM_025257.3	ENSP00000229729.6
SLC44A4	ENST00000414427.1 link	c.780-32G>A		intron_variant	Intron 10 of 12	5		ENSP00000398901.1

Frequencies

GnomAD3 genomes

AF:

0.0437

AC:

6650

AN:

152096

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0882

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.0225

Gnomad SAS

AF:

0.0136

Gnomad FIN

AF:

0.0339

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0279

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0294

AC:

6249

AN:

212664

AF XY:

0.0277

show subpopulations

Gnomad AFR exome

AF:

0.0896

Gnomad AMR exome

AF:

0.0223

Gnomad ASJ exome

AF:

0.0400

Gnomad EAS exome

AF:

0.0209

Gnomad FIN exome

AF:

0.0328

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0276

GnomAD4 exome

AF:

0.0254

AC:

35379

AN:

1390382

Hom.:

650

Cov.:

AF XY:

0.0251

AC XY:

17311

AN XY:

690108

show subpopulations

African (AFR)

AF:

0.0853

AC:

2723

AN:

31930

American (AMR)

AF:

0.0230

AC:

932

AN:

40610

Ashkenazi Jewish (ASJ)

AF:

0.0404

AC:

962

AN:

23796

East Asian (EAS)

AF:

0.0127

AC:

496

AN:

39010

South Asian (SAS)

AF:

0.0155

AC:

1234

AN:

79820

European-Finnish (FIN)

AF:

0.0312

AC:

1597

AN:

51128

Middle Eastern (MID)

AF:

0.0224

AC:

124

AN:

5526

European-Non Finnish (NFE)

AF:

0.0242

AC:

25716

AN:

1060832

Other (OTH)

AF:

0.0276

AC:

1595

AN:

57730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1763

3526

5290

7053

8816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

940

1880

2820

3760

4700

<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:

0.0437

AC:

6654

AN:

152214

Hom.:

212

Cov.:

AF XY:

0.0432

AC XY:

3213

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0882

AC:

3660

AN:

41512

American (AMR)

AF:

0.0212

AC:

324

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0366

AC:

127

AN:

3468

East Asian (EAS)

AF:

0.0226

AC:

117

AN:

5180

South Asian (SAS)

AF:

0.0134

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0339

AC:

359

AN:

10600

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0279

AC:

1896

AN:

68010

Other (OTH)

AF:

0.0407

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

324

647

971

1294

1618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0340

Hom.:

457

Bravo

AF:

0.0459

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 17, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.059

(source)

DANN

Benign

0.70

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over