rs149411

Variant names:

• chr12-50986449-A-G
• rs149411
• NM_000617.3:c.*1876T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001174125.2(SLC11A2):​c.*1876T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,283,976 control chromosomes in the GnomAD database, including 208,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21912 hom., cov: 32)
  • Exomes 𝑓: 0.57 (186874 hom.)
• Consequence: SLC11A2 NM_001174125.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.274
• Publications: 20 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-50986449-A-G is Benign according to our data. Variant chr12-50986449-A-G is described in ClinVar as Benign. ClinVar VariationId is 309281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174125.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	NM_000617.3	MANE Select	c.*1876T>C		3_prime_UTR	Exon 16 of 16	NP_000608.1
	SLC11A2	NM_001174125.2		c.*1876T>C		3_prime_UTR	Exon 16 of 16	NP_001167596.1
	SLC11A2	NM_001379455.1		c.*1876T>C		3_prime_UTR	Exon 17 of 17	NP_001366384.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	ENST00000262052.9	TSL:1 MANE Select	c.*1876T>C		3_prime_UTR	Exon 16 of 16	ENSP00000262052.5
	SLC11A2	ENST00000394904.9	TSL:1	c.*1876T>C		3_prime_UTR	Exon 16 of 16	ENSP00000378364.3
	SLC11A2	ENST00000547198.5	TSL:1	c.1629+1933T>C		intron	N/A	ENSP00000446769.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79695 AN: 151848 Hom.: 21905 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.543 AC: 69862 AN: 128744 AF XY: 0.525

Gnomad AFR exome AF: 0.376

Gnomad AMR exome AF: 0.677

Gnomad ASJ exome AF: 0.580

Gnomad EAS exome AF: 0.366

Gnomad FIN exome AF: 0.641

Gnomad NFE exome AF: 0.598

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.569 AC: 644075 AN: 1132010 Hom.: 186874 Cov.: 32 AF XY: 0.562 AC XY: 312148 AN XY: 555408

African (AFR) AF: 0.358 AC: 8679 AN: 24260

American (AMR) AF: 0.676 AC: 19052 AN: 28172

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 9169 AN: 15906

East Asian (EAS) AF: 0.369 AC: 4730 AN: 12816

South Asian (SAS) AF: 0.367 AC: 27903 AN: 75928

European-Finnish (FIN) AF: 0.632 AC: 7989 AN: 12638

Middle Eastern (MID) AF: 0.465 AC: 1286 AN: 2764

European-Non Finnish (NFE) AF: 0.591 AC: 542870 AN: 918288

Other (OTH) AF: 0.543 AC: 22397 AN: 41238

GnomAD4 genome AF: 0.525 AC: 79731 AN: 151966 Hom.: 21912 Cov.: 32 AF XY: 0.525 AC XY: 38962 AN XY: 74284

African (AFR) AF: 0.381 AC: 15826 AN: 41492

American (AMR) AF: 0.626 AC: 9563 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1983 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1927 AN: 5182

South Asian (SAS) AF: 0.354 AC: 1707 AN: 4816

European-Finnish (FIN) AF: 0.641 AC: 6771 AN: 10566

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40328 AN: 67854

Other (OTH) AF: 0.539 AC: 1138 AN: 2110

Alfa AF: 0.573 Hom.: 108922

Bravo AF: 0.522

Asia WGS AF: 0.408 AC: 1416 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Microcytic anemia with liver iron overload (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.66
PhyloP100		0.27
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: rs149411; hg19: chr12-51380232;