chr12-50986530-C-T

Variant names:

• chr12-50986530-C-T
• rs750648046
• NM_000617.3:c.*1795G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_000617.3(SLC11A2):​c.*1795G>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 0.000689 in 1,282,822 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (2 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.991
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000204 (31/151802) while in subpopulation NFE AF = 0.000369 (25/67718). AF 95% confidence interval is 0.000257. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 at 2 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.*1795G>A		3_prime_UTR	Exon 16 of 16	NP_000608.1	P49281-2
	SLC11A2	NM_001174125.2		c.*1795G>A		3_prime_UTR	Exon 16 of 16	NP_001167596.1	P49281-3
	SLC11A2	NM_001379455.1		c.*1795G>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.*1795G>A		3_prime_UTR	Exon 16 of 16	ENSP00000262052.5	P49281-2
	SLC11A2	ENST00000394904.9	TSL:1	c.*1795G>A		3_prime_UTR	Exon 16 of 16	ENSP00000378364.3	P49281-3
	SLC11A2	ENST00000547198.5	TSL:1	c.1629+1852G>A		intron	N/A	ENSP00000446769.1	P49281-1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 151802 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000369

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000292 AC: 38 AN: 130170 AF XY: 0.000352

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000411

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000748

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000754 AC: 853 AN: 1131020 Hom.: 2 Cov.: 34 AF XY: 0.000777 AC XY: 431 AN XY: 554874

African (AFR) AF: 0.0000822 AC: 2 AN: 24330

American (AMR) AF: 0.0000708 AC: 2 AN: 28252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15938

East Asian (EAS) AF: 0.00 AC: 0 AN: 12838

South Asian (SAS) AF: 0.00 AC: 0 AN: 76086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2770

European-Non Finnish (NFE) AF: 0.000908 AC: 833 AN: 916918

Other (OTH) AF: 0.000388 AC: 16 AN: 41262

GnomAD4 genome AF: 0.000204 AC: 31 AN: 151802 Hom.: 0 Cov.: 32 AF XY: 0.000189 AC XY: 14 AN XY: 74182

African (AFR) AF: 0.000121 AC: 5 AN: 41412

American (AMR) AF: 0.0000655 AC: 1 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000369 AC: 25 AN: 67718

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000641 Hom.: 0

Bravo AF: 0.000234

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Microcytic anemia with liver iron overload (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.93
DANN	Benign	0.56
PhyloP100		-0.99

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: rs750648046; hg19: chr12-51380313;