rs224446

Variant names:

• chr12-50987935-C-T
• rs224446
• NM_000617.3:c.*390G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-50987935-C-T
• chr12-50987935-C-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.*390G>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 0.165 in 1,279,300 control chromosomes in the GnomAD database, including 19,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2597 hom., cov: 32)
  • Exomes 𝑓: 0.16 (16676 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.576
• Publications: 14 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, 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=-0.79).
• BP6: Variant 12-50987935-C-T is Benign according to our data. Variant chr12-50987935-C-T is described in ClinVar as Benign. ClinVar VariationId is 309299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 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.*390G>A		3_prime_UTR	Exon 16 of 16	NP_000608.1	P49281-2
	SLC11A2	NM_001174125.2		c.*390G>A		3_prime_UTR	Exon 16 of 16	NP_001167596.1	P49281-3
	SLC11A2	NM_001379455.1		c.*390G>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.*390G>A		3_prime_UTR	Exon 16 of 16	ENSP00000262052.5	P49281-2
	SLC11A2	ENST00000394904.9	TSL:1	c.*390G>A		3_prime_UTR	Exon 16 of 16	ENSP00000378364.3	P49281-3
	SLC11A2	ENST00000547198.5	TSL:1	c.1629+447G>A		intron	N/A	ENSP00000446769.1	P49281-1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25837 AN: 152014 Hom.: 2597 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.205 AC: 26110 AN: 127490 AF XY: 0.210

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.155

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.501

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.165 AC: 185774 AN: 1127168 Hom.: 16676 Cov.: 26 AF XY: 0.169 AC XY: 93222 AN XY: 552836

African (AFR) AF: 0.127 AC: 3049 AN: 24092

American (AMR) AF: 0.155 AC: 4270 AN: 27536

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 3275 AN: 15938

East Asian (EAS) AF: 0.496 AC: 6394 AN: 12890

South Asian (SAS) AF: 0.263 AC: 19664 AN: 74694

European-Finnish (FIN) AF: 0.182 AC: 2309 AN: 12686

Middle Eastern (MID) AF: 0.173 AC: 474 AN: 2742

European-Non Finnish (NFE) AF: 0.152 AC: 138981 AN: 915492

Other (OTH) AF: 0.179 AC: 7358 AN: 41098

GnomAD4 genome AF: 0.170 AC: 25847 AN: 152132 Hom.: 2597 Cov.: 32 AF XY: 0.176 AC XY: 13091 AN XY: 74358

African (AFR) AF: 0.128 AC: 5310 AN: 41480

American (AMR) AF: 0.159 AC: 2425 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3472

East Asian (EAS) AF: 0.496 AC: 2567 AN: 5172

South Asian (SAS) AF: 0.288 AC: 1388 AN: 4824

European-Finnish (FIN) AF: 0.189 AC: 1997 AN: 10578

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10719 AN: 68004

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.158 Hom.: 2549

Bravo AF: 0.165

Asia WGS AF: 0.356 AC: 1239 AN: 3474

ClinVar

ClinVar submissions

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	-0.79
CADD	Benign	7.4
DANN	Benign	0.50
PhyloP100		0.58
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: rs224446; hg19: chr12-51381718;