Genetic Variant SLC39A1:c.-140+732G>A (chr1-153966654-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014437.5(SLC39A1):c.-140+732G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,874 control chromosomes in the GnomAD database, including 26,792 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 0.58 ( 26788 hom., cov: 32)

Exomes 𝑓: 0.50 ( 4 hom. )

Consequence

SLC39A1
NM_014437.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

Publications

25 publications found

Variant links:

Genes affected

SLC39A1 (HGNC:12876): (solute carrier family 39 member 1) This gene encodes a member of the zinc-iron permease family. The encoded protein is localized to the cell membrane and acts as a zinc uptake transporter. This gene has been linked to prostate cancer, breast cancer, and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

SLC39A1 links:

ENSG00000285779 (HGNC:):

ENSG00000285779 links:

CREB3L4 (HGNC:18854): (cAMP responsive element binding protein 3 like 4) This gene encodes a CREB (cAMP responsive element binding) protein with a transmembrane domain which localizes it to the ER membrane. The encoded protein is a transcriptional activator which contains a dimerization domain, and this protein may function in a number of processing pathways including protein processing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

CREB3L4 links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014437.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A1	NM_001271960.2		c.-140+1430G>A		intron	N/A	NP_001258889.1	Q9NY26-1
	SLC39A1	NM_014437.5		c.-140+732G>A		intron	N/A	NP_055252.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC39A1	ENST00000310483.10	TSL:1	c.-140+732G>A	intron	N/A	ENSP00000309710.6	Q9NY26-1
ENSG00000285779	ENST00000648921.1		n.193-2951G>A	intron	N/A	ENSP00000498105.1	A0A3B3ITX8
CREB3L4	ENST00000885128.1		c.-4-1868C>T	intron	N/A	ENSP00000555187.1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88074

AN:

151736

Hom.:

26738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.709

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.941

Gnomad SAS

AF:

0.651

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.564

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.557

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.357

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.563

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.581

AC:

88179

AN:

151854

Hom.:

26788

Cov.:

AF XY:

0.589

AC XY:

43744

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.709

AC:

29374

AN:

41420

American (AMR)

AF:

0.653

AC:

9946

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1465

AN:

3468

East Asian (EAS)

AF:

0.941

AC:

4858

AN:

5162

South Asian (SAS)

AF:

0.650

AC:

3137

AN:

4824

European-Finnish (FIN)

AF:

0.553

AC:

5829

AN:

10534

Middle Eastern (MID)

AF:

0.568

AC:

166

AN:

292

European-Non Finnish (NFE)

AF:

0.468

AC:

31770

AN:

67896

Other (OTH)

AF:

0.555

AC:

1172

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1793

3585

5378

7170

8963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.530

Hom.:

34885

Bravo

AF:

0.598

Asia WGS

AF:

0.762

AC:

2648

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

(source)

DANN

Benign

0.57

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over