12-50980965-G-T

Variant summary

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

The ENST00000546636.5(SLC11A2):c.*87+674C>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,148 control chromosomes in the GnomAD database, including 42,071 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 (42071 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SLC11A2 ENST00000546636.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_001174126.2	c.*761C>A		3_prime_UTR_variant	17/17
SLC11A2	NM_001174127.2	c.*761C>A		3_prime_UTR_variant	17/17
SLC11A2	NM_001379446.1	c.*761C>A		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000546636.5	c.*87+674C>A		intron_variant, NMD_transcript_variant		1
SLC11A2	ENST00000547688.7	c.*761C>A		3_prime_UTR_variant	17/17	5
SLC11A2	ENST00000643884.1	c.*864C>A		3_prime_UTR_variant	18/18

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112592 AN: 152030 Hom.: 42042 Cov.: 33

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.741

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.740 AC: 112664 AN: 152148 Hom.: 42071 Cov.: 33 AF XY: 0.745 AC XY: 55425 AN XY: 74374

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.831

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.743

Alfa AF: 0.743 Hom.: 9359

Bravo AF: 0.740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.6
Dann	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs829022; hg19: chr12-51374748;