Genetic Variant ENST00000310483.10: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 ENST00000310483.10(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
ENST00000310483.10 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:

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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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
SLC39A1	NM_001271960.2 link	c.-140+1430G>A	intron_variant	Intron 1 of 4	NP_001258889.1	Q9NY26-1
SLC39A1	NM_014437.5 link	c.-140+732G>A	intron_variant	Intron 1 of 4	NP_055252.2	Q9NY26-1
SLC39A1	XM_047418008.1 link	c.-242+732G>A	intron_variant	Intron 1 of 4	XP_047273964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285779	ENST00000648921.1 link	n.193-2951G>A		intron_variant	Intron 2 of 5			ENSP00000498105.1		A0A3B3ITX8

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over