Genetic Variant NM_000617.3:c.*1261G>A (chr12-50987064-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000617.3(SLC11A2):c.*1261G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,286,404 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 20 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 4 hom. )

Consequence

SLC11A2
NM_000617.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.535

Publications

1 publications found

Variant links:

Genes affected

SLC11A2 (HGNC:10908): (solute carrier family 11 member 2) This gene encodes a member of the solute carrier family 11 protein family. The product of this gene transports divalent metals and is involved in iron absorption. Mutations in this gene are associated with hypochromic microcytic anemia with iron overload. A related solute carrier family 11 protein gene is located on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2010]

SLC11A2 Gene-Disease associations (from GenCC):

microcytic anemia with liver iron overload
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, Genomics England PanelApp

SLC11A2 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=-0.81).

BP6

Variant 12-50987064-C-T is Benign according to our data. Variant chr12-50987064-C-T is described in ClinVar as Benign. ClinVar VariationId is 309288.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00705 (1074/152272) while in subpopulation AFR AF = 0.0241 (1000/41562). AF 95% confidence interval is 0.0228. There are 20 homozygotes in GnomAd4. There are 502 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000617.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC11A2	NM_000617.3	MANE Select	c.*1261G>A	3_prime_UTR	Exon 16 of 16	NP_000608.1	P49281-2
SLC11A2	NM_001174125.2		c.*1261G>A	3_prime_UTR	Exon 16 of 16	NP_001167596.1	P49281-3
SLC11A2	NM_001379455.1		c.*1261G>A	3_prime_UTR	Exon 17 of 17	NP_001366384.1	P49281-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC11A2	ENST00000262052.9	TSL:1 MANE Select	c.*1261G>A	3_prime_UTR	Exon 16 of 16	ENSP00000262052.5	P49281-2
SLC11A2	ENST00000394904.9	TSL:1	c.*1261G>A	3_prime_UTR	Exon 16 of 16	ENSP00000378364.3	P49281-3
SLC11A2	ENST00000547198.5	TSL:1	c.1629+1318G>A	intron	N/A	ENSP00000446769.1	P49281-1

Frequencies

GnomAD3 genomes

AF:

0.00687

AC:

1045

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00624

GnomAD2 exomes

AF:

0.00143

AC:

185

AN:

129532

AF XY:

0.00115

show subpopulations

Gnomad AFR exome

AF:

0.0244

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000809

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.000680

AC:

771

AN:

1134132

Hom.:

Cov.:

AF XY:

0.000615

AC XY:

342

AN XY:

556270

show subpopulations

African (AFR)

AF:

0.0226

AC:

550

AN:

24298

American (AMR)

AF:

0.00103

AC:

AN:

28142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15898

East Asian (EAS)

AF:

0.0000779

AC:

AN:

12834

South Asian (SAS)

AF:

0.0000922

AC:

AN:

75914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12612

Middle Eastern (MID)

AF:

0.00471

AC:

AN:

2758

European-Non Finnish (NFE)

AF:

0.000101

AC:

AN:

920390

Other (OTH)

AF:

0.00189

AC:

AN:

41286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00705

AC:

1074

AN:

152272

Hom.:

Cov.:

AF XY:

0.00674

AC XY:

502

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0241

AC:

1000

AN:

41562

American (AMR)

AF:

0.00327

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68016

Other (OTH)

AF:

0.00618

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

108

163

217

271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00390

Hom.:

Bravo

AF:

0.00793

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Microcytic anemia with liver iron overload (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.5

(source)

DANN

Benign

0.62

PhyloP100

0.54

Mutation Taster

=100/0

polymorphism

(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