rs2018673

Variant names:

• chr12-50992747-G-A
• rs2018673
• NM_000617.3:c.1197+63C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-50992747-G-A
• chr12-50992747-G-T

Variant summary

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

The NM_000617.3(SLC11A2):​c.1197+63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.54 (19999 hom., cov: 17)
  • Exomes 𝑓: 0.45 (44083 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A2	NM_000617.3	c.1197+63C>T		intron_variant	Intron 12 of 15	ENST00000262052.9	NP_000608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A2	ENST00000262052.9	c.1197+63C>T		intron_variant	Intron 12 of 15	1	NM_000617.3	ENSP00000262052.5

Frequencies

GnomAD3 genomes AF: 0.542 AC: 68151 AN: 125770 Hom.: 19995 Cov.: 17

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.467

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.549

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.448 AC: 356742 AN: 797078 Hom.: 44083 AF XY: 0.453 AC XY: 180524 AN XY: 398770

African (AFR) AF: 0.432 AC: 7258 AN: 16796

American (AMR) AF: 0.563 AC: 11015 AN: 19554

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 6448 AN: 13552

East Asian (EAS) AF: 0.351 AC: 8540 AN: 24354

South Asian (SAS) AF: 0.456 AC: 20368 AN: 44668

European-Finnish (FIN) AF: 0.533 AC: 12230 AN: 22954

Middle Eastern (MID) AF: 0.420 AC: 968 AN: 2304

European-Non Finnish (NFE) AF: 0.443 AC: 274681 AN: 619410

Other (OTH) AF: 0.455 AC: 15234 AN: 33486

GnomAD4 genome AF: 0.542 AC: 68150 AN: 125768 Hom.: 19999 Cov.: 17 AF XY: 0.529 AC XY: 31103 AN XY: 58814

African (AFR) AF: 0.506 AC: 16772 AN: 33162

American (AMR) AF: 0.586 AC: 6359 AN: 10846

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1842 AN: 3236

East Asian (EAS) AF: 0.348 AC: 1593 AN: 4578

South Asian (SAS) AF: 0.361 AC: 1474 AN: 4086

European-Finnish (FIN) AF: 0.439 AC: 2098 AN: 4776

Middle Eastern (MID) AF: 0.470 AC: 109 AN: 232

European-Non Finnish (NFE) AF: 0.588 AC: 36618 AN: 62252

Other (OTH) AF: 0.548 AC: 942 AN: 1720

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.48
DANN	Benign	0.51
PhyloP100		-0.96
Mutation Taster		=12/88	disease causing (long InDel)

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: rs2018673; hg19: chr12-51386530; COSMIC: COSV50370282; COSMIC: COSV50370282;