rs224568

Variant names:

• chr12-50992765-A-G
• rs224568
• NM_000617.3:c.1197+45T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000262052.9(SLC11A2):​c.1197+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,595,918 control chromosomes in the GnomAD database, including 24,361 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 0.15 (2208 hom., cov: 28)
  • Exomes 𝑓: 0.16 (22153 hom.)
• Consequence: SLC11A2 ENST00000262052.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262052.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	NM_000617.3	MANE Select	c.1197+45T>C		intron	N/A	NP_000608.1
	SLC11A2	NM_001379446.1		c.1284+45T>C		intron	N/A	NP_001366375.1
	SLC11A2	NM_001174125.2		c.1284+45T>C		intron	N/A	NP_001167596.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	ENST00000262052.9	TSL:1 MANE Select	c.1197+45T>C		intron	N/A	ENSP00000262052.5
	SLC11A2	ENST00000394904.9	TSL:1	c.1284+45T>C		intron	N/A	ENSP00000378364.3
	SLC11A2	ENST00000547198.5	TSL:1	c.1197+45T>C		intron	N/A	ENSP00000446769.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22924 AN: 150484 Hom.: 2209 Cov.: 28

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.175 AC: 42220 AN: 240628 AF XY: 0.179

Gnomad AFR exome AF: 0.0835

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.189

Gnomad EAS exome AF: 0.455

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.164 AC: 237392 AN: 1445328 Hom.: 22153 Cov.: 28 AF XY: 0.167 AC XY: 120101 AN XY: 719544

African (AFR) AF: 0.0814 AC: 2696 AN: 33114

American (AMR) AF: 0.149 AC: 6544 AN: 43850

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 5148 AN: 25866

East Asian (EAS) AF: 0.445 AC: 17582 AN: 39528

South Asian (SAS) AF: 0.234 AC: 19817 AN: 84672

European-Finnish (FIN) AF: 0.181 AC: 9582 AN: 53066

Middle Eastern (MID) AF: 0.154 AC: 869 AN: 5654

European-Non Finnish (NFE) AF: 0.150 AC: 164974 AN: 1099874

Other (OTH) AF: 0.171 AC: 10180 AN: 59704

GnomAD4 genome AF: 0.152 AC: 22930 AN: 150590 Hom.: 2208 Cov.: 28 AF XY: 0.157 AC XY: 11502 AN XY: 73330

African (AFR) AF: 0.0843 AC: 3468 AN: 41120

American (AMR) AF: 0.148 AC: 2239 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 698 AN: 3452

East Asian (EAS) AF: 0.459 AC: 2323 AN: 5066

South Asian (SAS) AF: 0.255 AC: 1218 AN: 4768

European-Finnish (FIN) AF: 0.179 AC: 1803 AN: 10092

Middle Eastern (MID) AF: 0.215 AC: 62 AN: 288

European-Non Finnish (NFE) AF: 0.155 AC: 10505 AN: 67738

Other (OTH) AF: 0.150 AC: 312 AN: 2078

Alfa AF: 0.157 Hom.: 1122

Bravo AF: 0.148

Asia WGS AF: 0.320 AC: 1114 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.63
PhyloP100		0.39
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: rs224568; hg19: chr12-51386548; COSMIC: COSV50369700; COSMIC: COSV50369700;