chr12-50986958-A-G

Variant names:

• chr12-50986958-A-G
• rs1235162595
• NM_000617.3:c.*1367T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_000617.3(SLC11A2):​c.*1367T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000932 in 1,287,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.106
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00000969 (11/1134864) while in subpopulation MID AF = 0.00144 (4/2770). AF 95% confidence interval is 0.000493. There are 0 homozygotes in GnomAdExome4. There are 8 alleles in the male GnomAdExome4 subpopulation. Median coverage is 35. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.*1367T>C		3_prime_UTR	Exon 16 of 16	NP_000608.1	P49281-2
	SLC11A2	NM_001174125.2		c.*1367T>C		3_prime_UTR	Exon 16 of 16	NP_001167596.1	P49281-3
	SLC11A2	NM_001379455.1		c.*1367T>C		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.*1367T>C		3_prime_UTR	Exon 16 of 16	ENSP00000262052.5	P49281-2
	SLC11A2	ENST00000394904.9	TSL:1	c.*1367T>C		3_prime_UTR	Exon 16 of 16	ENSP00000378364.3	P49281-3
	SLC11A2	ENST00000547198.5	TSL:1	c.1629+1424T>C		intron	N/A	ENSP00000446769.1	P49281-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00000969 AC: 11 AN: 1134864 Hom.: 0 Cov.: 35 AF XY: 0.0000144 AC XY: 8 AN XY: 556694

African (AFR) AF: 0.00 AC: 0 AN: 24338

American (AMR) AF: 0.00 AC: 0 AN: 28256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15934

East Asian (EAS) AF: 0.00 AC: 0 AN: 12840

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12640

Middle Eastern (MID) AF: 0.00144 AC: 4 AN: 2770

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920648

Other (OTH) AF: 0.000145 AC: 6 AN: 41336

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

ClinVar

ClinVar submissions

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	-0.89
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		-0.11

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: rs1235162595; hg19: chr12-51380741;