rs2279014

Variant names:

• chr2-218396453-C-T
• rs2279014
• NM_000578.4:c.*1418C>T

Variant summary

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

The NM_000578.4(SLC11A1):​c.*1418C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,336 control chromosomes in the GnomAD database, including 10,459 homozygotes. 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 0.37 (10449 hom., cov: 34)
  • Exomes 𝑓: 0.38 (10 hom.)
• Consequence: SLC11A1 NM_000578.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 31 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]

CTDSP1 (HGNC:21614): (CTD small phosphatase 1) This gene encodes a member of the small C-terminal domain phosphatase (SCP) family of nuclear phosphatases. These proteins play a role in transcriptional regulation through specific dephosphorylation of phosphoserine 5 within tandem heptapeptide repeats of the C-terminal domain of RNA polymerase II. The encoded protein plays a role in neuronal gene silencing in non-neuronal cells, and may also inhibit osteoblast differentiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000578.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	NM_000578.4	MANE Select	c.*1418C>T		3_prime_UTR	Exon 15 of 15	NP_000569.3
	CTDSP1	NR_174456.1		n.103C>T		non_coding_transcript_exon	Exon 1 of 7
	CTDSP1	NR_174457.1		n.103C>T		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	ENST00000233202.11	TSL:1 MANE Select	c.*1418C>T		3_prime_UTR	Exon 15 of 15	ENSP00000233202.6

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55912 AN: 152040 Hom.: 10440 Cov.: 34

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.376 AC: 67 AN: 178 Hom.: 10 Cov.: 0 AF XY: 0.373 AC XY: 44 AN XY: 118

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.377 AC: 49 AN: 130

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.386 AC: 17 AN: 44

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.368 AC: 55961 AN: 152158 Hom.: 10449 Cov.: 34 AF XY: 0.365 AC XY: 27181 AN XY: 74390

African (AFR) AF: 0.412 AC: 17107 AN: 41528

American (AMR) AF: 0.381 AC: 5826 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3468

East Asian (EAS) AF: 0.265 AC: 1371 AN: 5170

South Asian (SAS) AF: 0.268 AC: 1291 AN: 4824

European-Finnish (FIN) AF: 0.334 AC: 3532 AN: 10588

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24610 AN: 67962

Other (OTH) AF: 0.368 AC: 777 AN: 2112

Alfa AF: 0.362 Hom.: 18039

Bravo AF: 0.376

Asia WGS AF: 0.284 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.82
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

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: rs2279014; hg19: chr2-219261176; COSMIC: COSV51919151; COSMIC: COSV51919151;