12-51017570-G-T

Variant names:

• chr12-51017570-G-T
• rs407135
• NM_000617.3:c.-38-6804C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000617.3(SLC11A2):​c.-38-6804C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,078 control chromosomes in the GnomAD database, including 42,212 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 0.74 (42212 hom., cov: 31)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598
• Publications: 12 publications found

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: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A2	NM_000617.3	c.-38-6804C>A		intron_variant	Intron 1 of 15	ENST00000262052.9	NP_000608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A2	ENST00000262052.9	c.-38-6804C>A		intron_variant	Intron 1 of 15	1	NM_000617.3	ENSP00000262052.5

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112782 AN: 151960 Hom.: 42184 Cov.: 31

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.740

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.742 AC: 112854 AN: 152078 Hom.: 42212 Cov.: 31 AF XY: 0.747 AC XY: 55514 AN XY: 74318

African (AFR) AF: 0.673 AC: 27909 AN: 41462

American (AMR) AF: 0.802 AC: 12236 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2690 AN: 3470

East Asian (EAS) AF: 0.869 AC: 4504 AN: 5182

South Asian (SAS) AF: 0.643 AC: 3099 AN: 4820

European-Finnish (FIN) AF: 0.831 AC: 8790 AN: 10582

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51185 AN: 67976

Other (OTH) AF: 0.742 AC: 1569 AN: 2114

Alfa AF: 0.748 Hom.: 7329

Bravo AF: 0.741

Asia WGS AF: 0.770 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.28
DANN	Benign	0.30
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs407135; hg19: chr12-51411353;