Genetic Variant NM_014585.6:c.1402+117C>T (chr2-189563467-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014585.6(SLC40A1):c.1402+117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 842,504 control chromosomes in the GnomAD database, including 4,494 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 0.078 ( 651 hom., cov: 32)

Exomes 𝑓: 0.10 ( 3843 hom. )

Consequence

SLC40A1
NM_014585.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.690

Publications

4 publications found

Variant links:

Genes affected

SLC40A1 (HGNC:10909): (solute carrier family 40 member 1) The protein encoded by this gene is a cell membrane protein that may be involved in iron export from duodenal epithelial cells. Defects in this gene are a cause of hemochromatosis type 4 (HFE4). [provided by RefSeq, Jul 2008]

SLC40A1 Gene-Disease associations (from GenCC):

hemochromatosis type 4
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

SLC40A1 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=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014585.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC40A1	NM_014585.6	MANE Select	c.1402+117C>T		intron	N/A	NP_055400.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC40A1	ENST00000261024.7	TSL:1 MANE Select	c.1402+117C>T		intron	N/A	ENSP00000261024.3

Frequencies

GnomAD3 genomes

AF:

0.0784

AC:

11913

AN:

151948

Hom.:

645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0294

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.0631

Gnomad ASJ

AF:

0.0743

Gnomad EAS

AF:

0.0190

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.0941

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0810

GnomAD4 exome

AF:

0.100

AC:

69124

AN:

690442

Hom.:

3843

AF XY:

0.102

AC XY:

35956

AN XY:

351280

show subpopulations

African (AFR)

AF:

0.0262

AC:

435

AN:

16576

American (AMR)

AF:

0.0548

AC:

986

AN:

18008

Ashkenazi Jewish (ASJ)

AF:

0.0712

AC:

1102

AN:

15468

East Asian (EAS)

AF:

0.0259

AC:

827

AN:

31904

South Asian (SAS)

AF:

0.168

AC:

7114

AN:

42248

European-Finnish (FIN)

AF:

0.0949

AC:

3844

AN:

40512

Middle Eastern (MID)

AF:

0.0938

AC:

241

AN:

2568

European-Non Finnish (NFE)

AF:

0.105

AC:

51479

AN:

489860

Other (OTH)

AF:

0.0930

AC:

3096

AN:

33298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3052

6105

9157

12210

15262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1386

2772

4158

5544

6930

<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:

0.0785

AC:

11930

AN:

152062

Hom.:

651

Cov.:

AF XY:

0.0791

AC XY:

5877

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0294

AC:

1219

AN:

41496

American (AMR)

AF:

0.0630

AC:

962

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0743

AC:

258

AN:

3472

East Asian (EAS)

AF:

0.0189

AC:

AN:

5186

South Asian (SAS)

AF:

0.178

AC:

856

AN:

4820

European-Finnish (FIN)

AF:

0.0941

AC:

991

AN:

10536

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7225

AN:

67964

Other (OTH)

AF:

0.0873

AC:

184

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

556

1113

1669

2226

2782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.0981

Hom.:

1719

Bravo

AF:

0.0698

Asia WGS

AF:

0.127

AC:

440

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.27

(source)

DANN

Benign

0.50

PhyloP100

-0.69

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over