12-50986572-ATT-AT

Variant names:

• chr12-50986572-AT-A
• rs755515112
• NM_000617.3:c.*1752delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000617.3(SLC11A2):​c.*1752delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000912 in 1,170,700 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0034 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (1 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582
• Publications: 0 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00337 (505/149814) while in subpopulation AFR AF = 0.0116 (476/41000). AF 95% confidence interval is 0.0107. There are 4 homozygotes in GnomAd4. There are 220 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.*1752delA		3_prime_UTR	Exon 16 of 16	NP_000608.1	P49281-2
	SLC11A2	NM_001174125.2		c.*1752delA		3_prime_UTR	Exon 16 of 16	NP_001167596.1	P49281-3
	SLC11A2	NM_001379455.1		c.*1752delA		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.*1752delA		3_prime_UTR	Exon 16 of 16	ENSP00000262052.5	P49281-2
	SLC11A2	ENST00000394904.9	TSL:1	c.*1752delA		3_prime_UTR	Exon 16 of 16	ENSP00000378364.3	P49281-3
	SLC11A2	ENST00000547198.5	TSL:1	c.1629+1809delA		intron	N/A	ENSP00000446769.1	P49281-1

Frequencies

GnomAD3 genomes AF: 0.00337 AC: 505 AN: 149722 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000870

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000119

Gnomad OTH AF: 0.00294

GnomAD2 exomes AF: 0.00195 AC: 174 AN: 89444 AF XY: 0.00189

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.00229

Gnomad ASJ exome AF: 0.00105

Gnomad EAS exome AF: 0.00114

Gnomad FIN exome AF: 0.000797

Gnomad NFE exome AF: 0.000751

Gnomad OTH exome AF: 0.00110

GnomAD4 exome AF: 0.000551 AC: 563 AN: 1020886 Hom.: 1 Cov.: 35 AF XY: 0.000503 AC XY: 252 AN XY: 500862

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0135 AC: 294 AN: 21790

American (AMR) AF: 0.00160 AC: 39 AN: 24406

Ashkenazi Jewish (ASJ) AF: 0.000636 AC: 9 AN: 14150

East Asian (EAS) AF: 0.000174 AC: 2 AN: 11516

South Asian (SAS) AF: 0.000672 AC: 45 AN: 66954

European-Finnish (FIN) AF: 0.000357 AC: 4 AN: 11218

Middle Eastern (MID) AF: 0.00162 AC: 4 AN: 2476

European-Non Finnish (NFE) AF: 0.000170 AC: 141 AN: 831198

Other (OTH) AF: 0.000672 AC: 25 AN: 37178

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00337 AC: 505 AN: 149814 Hom.: 4 Cov.: 32 AF XY: 0.00301 AC XY: 220 AN XY: 73112

African (AFR) AF: 0.0116 AC: 476 AN: 41000

American (AMR) AF: 0.000869 AC: 13 AN: 14962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4658

European-Finnish (FIN) AF: 0.000197 AC: 2 AN: 10162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000119 AC: 8 AN: 67216

Other (OTH) AF: 0.00291 AC: 6 AN: 2064

Alfa AF: 0.0110 Hom.: 0

Bravo AF: 0.00374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism

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: rs755515112; hg19: chr12-51380355; COSMIC: COSV50373857; COSMIC: COSV50373857;