2-218384290-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000578.4(SLC11A1):c.198C>T(p.Phe66=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,607,394 control chromosomes in the GnomAD database, including 54,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (4358 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49910 hom.)
• Consequence: SLC11A1 NM_000578.4 synonymous
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 0.710

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A1	NM_000578.4	c.198C>T	p.Phe66=	synonymous_variant	3/15	ENST00000233202.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A1	ENST00000233202.11	c.198C>T	p.Phe66=	synonymous_variant	3/15	1	NM_000578.4	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35352 AN: 152094 Hom.: 4355 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.253

GnomAD3 exomes AF: 0.235 AC: 58512 AN: 249308 Hom.: 7446 AF XY: 0.231 AC XY: 31090 AN XY: 134800

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.114

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.254

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.257 AC: 374160 AN: 1455182 Hom.: 49910 Cov.: 32 AF XY: 0.253 AC XY: 183007 AN XY: 723982

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.306

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.232 AC: 35376 AN: 152212 Hom.: 4358 Cov.: 32 AF XY: 0.231 AC XY: 17163 AN XY: 74402

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.253

Alfa AF: 0.262 Hom.: 10721

Bravo AF: 0.237

Asia WGS AF: 0.123 AC: 427 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Mycobacterium tuberculosis, susceptibility to infection by Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Aug 23, 2005

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	12
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2276631; hg19: chr2-219249013; COSMIC: COSV51915749; COSMIC: COSV51915749;