NM_000617.3:c.*1031G>A

Variant names:

• chr12-50987294-C-T
• rs150909
• NM_000617.3:c.*1031G>A

Variant summary

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

The NM_000617.3(SLC11A2):​c.*1031G>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 0.932 in 1,287,120 control chromosomes in the GnomAD database, including 559,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (63322 hom., cov: 32)
  • Exomes 𝑓: 0.93 (496068 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.01
• 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: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-50987294-C-T is Benign according to our data. Variant chr12-50987294-C-T is described in ClinVar as Benign. ClinVar VariationId is 309290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	NM_000617.3	MANE Select	c.*1031G>A		3_prime_UTR	Exon 16 of 16	NP_000608.1	P49281-2
	SLC11A2	NM_001174125.2		c.*1031G>A		3_prime_UTR	Exon 16 of 16	NP_001167596.1	P49281-3
	SLC11A2	NM_001379455.1		c.*1031G>A		3_prime_UTR	Exon 17 of 17	NP_001366384.1	P49281-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	ENST00000262052.9	TSL:1 MANE Select	c.*1031G>A		3_prime_UTR	Exon 16 of 16	ENSP00000262052.5	P49281-2
	SLC11A2	ENST00000394904.9	TSL:1	c.*1031G>A		3_prime_UTR	Exon 16 of 16	ENSP00000378364.3	P49281-3
	SLC11A2	ENST00000547198.5	TSL:1	c.1629+1088G>A		intron	N/A	ENSP00000446769.1	P49281-1

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138416 AN: 152114 Hom.: 63256 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.922

GnomAD2 exomes AF: 0.938 AC: 122336 AN: 130486 AF XY: 0.935

Gnomad AFR exome AF: 0.810

Gnomad AMR exome AF: 0.959

Gnomad ASJ exome AF: 0.947

Gnomad EAS exome AF: 0.980

Gnomad FIN exome AF: 0.979

Gnomad NFE exome AF: 0.940

Gnomad OTH exome AF: 0.940

GnomAD4 exome AF: 0.935 AC: 1060651 AN: 1134888 Hom.: 496068 Cov.: 56 AF XY: 0.934 AC XY: 520207 AN XY: 556700

African (AFR) AF: 0.797 AC: 19387 AN: 24340

American (AMR) AF: 0.959 AC: 27109 AN: 28258

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 15120 AN: 15938

East Asian (EAS) AF: 0.981 AC: 12598 AN: 12840

South Asian (SAS) AF: 0.909 AC: 69182 AN: 76110

European-Finnish (FIN) AF: 0.977 AC: 12347 AN: 12640

Middle Eastern (MID) AF: 0.905 AC: 2507 AN: 2770

European-Non Finnish (NFE) AF: 0.938 AC: 863920 AN: 920652

Other (OTH) AF: 0.931 AC: 38481 AN: 41340

GnomAD4 genome AF: 0.910 AC: 138539 AN: 152232 Hom.: 63322 Cov.: 32 AF XY: 0.914 AC XY: 68070 AN XY: 74440

African (AFR) AF: 0.816 AC: 33851 AN: 41496

American (AMR) AF: 0.941 AC: 14379 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3257 AN: 3472

East Asian (EAS) AF: 0.984 AC: 5090 AN: 5172

South Asian (SAS) AF: 0.909 AC: 4383 AN: 4824

European-Finnish (FIN) AF: 0.982 AC: 10438 AN: 10626

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64087 AN: 68040

Other (OTH) AF: 0.923 AC: 1949 AN: 2112

Alfa AF: 0.932 Hom.: 70547

Bravo AF: 0.902

Asia WGS AF: 0.945 AC: 3287 AN: 3478

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	-0.89
CADD	Benign	0.11
DANN	Benign	0.71
PhyloP100		-2.0
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: rs150909; hg19: chr12-51381077;