Genetic Variant NM_025257.3:c.40+733A>G (chr6-31878208-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025257.3(SLC44A4):c.40+733A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,506 control chromosomes in the GnomAD database, including 63,915 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 0.91 ( 63597 hom., cov: 28)

Exomes 𝑓: 0.91 ( 318 hom. )

Consequence

SLC44A4
NM_025257.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0880

Publications

41 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 links:

EHMT2-AS1 (HGNC:39751): (EHMT2 and SLC44A4 antisense RNA 1)

EHMT2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 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.40+733A>G	intron	N/A	NP_079533.2	A0A140VJH4
SLC44A4	NM_001178044.2		c.40+733A>G	intron	N/A	NP_001171515.1	Q53GD3-4
EHMT2-AS1	NR_174947.1		n.271+130T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC44A4	ENST00000229729.11	TSL:1 MANE Select	c.40+733A>G	intron	N/A	ENSP00000229729.6	Q53GD3-1
SLC44A4	ENST00000414427.1	TSL:5	c.25+733A>G	intron	N/A	ENSP00000398901.1	H0Y5I3
SLC44A4	ENST00000882851.1		c.40+733A>G	intron	N/A	ENSP00000552910.1

Frequencies

GnomAD3 genomes

AF:

0.914

AC:

138588

AN:

151632

Hom.:

63533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.974

Gnomad AMI

AF:

0.933

Gnomad AMR

AF:

0.935

Gnomad ASJ

AF:

0.968

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.974

Gnomad FIN

AF:

0.874

Gnomad MID

AF:

0.972

Gnomad NFE

AF:

0.864

Gnomad OTH

AF:

0.940

GnomAD4 exome

AF:

0.914

AC:

691

AN:

756

Hom.:

318

AF XY:

0.919

AC XY:

566

AN XY:

616

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.901

AC:

564

AN:

626

Other (OTH)

AF:

0.964

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.914

AC:

138710

AN:

151750

Hom.:

63597

Cov.:

AF XY:

0.915

AC XY:

67862

AN XY:

74144

show subpopulations

African (AFR)

AF:

0.974

AC:

40304

AN:

41366

American (AMR)

AF:

0.936

AC:

14279

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.968

AC:

3358

AN:

3470

East Asian (EAS)

AF:

0.996

AC:

5101

AN:

5124

South Asian (SAS)

AF:

0.974

AC:

4677

AN:

4802

European-Finnish (FIN)

AF:

0.874

AC:

9242

AN:

10572

Middle Eastern (MID)

AF:

0.969

AC:

285

AN:

294

European-Non Finnish (NFE)

AF:

0.864

AC:

58635

AN:

67848

Other (OTH)

AF:

0.941

AC:

1982

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

592

1184

1776

2368

2960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<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:

0.888

Hom.:

202489

Bravo

AF:

0.922

Asia WGS

AF:

0.980

AC:

3410

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.088

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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