2-218383067-C-T

Variant names:

• chr2-218383067-C-T
• rs7576974
• NM_000578.4:c.115C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_000578.4(SLC11A1):​c.115C>T​(p.Leu39Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,613,940 control chromosomes in the GnomAD database, including 932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.043 (479 hom., cov: 31)
  • Exomes 𝑓: 0.0066 (453 hom.)
• Consequence: SLC11A1 NM_000578.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.133
• Publications: 6 publications found

Genes affected

SLC11A1 (HGNC:10907): (solute carrier family 11 member 1) This gene is a member of the solute carrier family 11 (proton-coupled divalent metal ion transporters) family and encodes a multi-pass membrane protein. The protein functions as a divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Mutations in this gene have been associated with susceptibility to infectious diseases such as tuberculosis and leprosy, and inflammatory diseases such as rheumatoid arthritis and Crohn disease. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

SLC11A1 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 2-218383067-C-T is Benign according to our data. Variant chr2-218383067-C-T is described in ClinVar as [Benign]. Clinvar id is 3055747.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.133 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A1	NM_000578.4	c.115C>T	p.Leu39Leu	synonymous_variant	Exon 2 of 15	ENST00000233202.11	NP_000569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11	c.115C>T	p.Leu39Leu	synonymous_variant	Exon 2 of 15	1	NM_000578.4	ENSP00000233202.6

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6554 AN: 152072 Hom.: 479 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00483

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.0349

GnomAD2 exomes AF: 0.0152 AC: 3771 AN: 248498 AF XY: 0.0122

Gnomad AFR exome AF: 0.149

Gnomad AMR exome AF: 0.0110

Gnomad ASJ exome AF: 0.0154

Gnomad EAS exome AF: 0.00577

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00131

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.00662 AC: 9674 AN: 1461750 Hom.: 453 Cov.: 31 AF XY: 0.00636 AC XY: 4625 AN XY: 727164

African (AFR) AF: 0.154 AC: 5170 AN: 33474

American (AMR) AF: 0.0119 AC: 531 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0160 AC: 419 AN: 26132

East Asian (EAS) AF: 0.00539 AC: 214 AN: 39696

South Asian (SAS) AF: 0.0152 AC: 1315 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.0186 AC: 107 AN: 5768

European-Non Finnish (NFE) AF: 0.000934 AC: 1038 AN: 1111936

Other (OTH) AF: 0.0146 AC: 880 AN: 60394

GnomAD4 genome AF: 0.0432 AC: 6581 AN: 152190 Hom.: 479 Cov.: 31 AF XY: 0.0416 AC XY: 3093 AN XY: 74426

African (AFR) AF: 0.142 AC: 5874 AN: 41486

American (AMR) AF: 0.0226 AC: 346 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3468

East Asian (EAS) AF: 0.00484 AC: 25 AN: 5164

South Asian (SAS) AF: 0.0178 AC: 86 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00150 AC: 102 AN: 68020

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

Alfa AF: 0.0195 Hom.: 431

Bravo AF: 0.0478

Asia WGS AF: 0.0340 AC: 118 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC11A1-related disorder Benign:1

Jan 28, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.0
DANN	Benign	0.73
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs7576974; hg19: chr2-219247790;