12-51022737-T-C

Position:

• chr12-51022737-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000617.3(SLC11A2):​c.-39+3573A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,052 control chromosomes in the GnomAD database, including 16,963 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 0.45 (16963 hom., cov: 32)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.-39+3573A>G		intron_variant		ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9	c.-39+3573A>G		intron_variant		1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68950 AN: 151934 Hom.: 16961 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.0909

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.454 AC: 68975 AN: 152052 Hom.: 16963 Cov.: 32 AF XY: 0.449 AC XY: 33338 AN XY: 74316

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.0912

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.470

Alfa AF: 0.532 Hom.: 37468

Bravo AF: 0.440

Asia WGS AF: 0.250 AC: 869 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs224572; hg19: chr12-51416520; COSMIC: COSV50375650;