2-218395121-A-G

Position:

• chr2-218395121-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000578.4(SLC11A1):​c.*86A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,035,212 control chromosomes in the GnomAD database, including 99,893 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 0.51 (22175 hom., cov: 32)
  • Exomes 𝑓: 0.41 (77718 hom.)
• Consequence: SLC11A1 NM_000578.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC11A1	NM_000578.4	c.*86A>G		3_prime_UTR_variant	15/15	ENST00000233202.11	NP_000569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11	c.*86A>G		3_prime_UTR_variant	15/15	1	NM_000578.4	ENSP00000233202.6

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77080 AN: 151834 Hom.: 22128 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.413 AC: 364529 AN: 883260 Hom.: 77718 Cov.: 11 AF XY: 0.408 AC XY: 184091 AN XY: 451324

Gnomad4 AFR exome AF: 0.811

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.415

Gnomad4 OTH exome AF: 0.426

GnomAD4 genome AF: 0.508 AC: 77202 AN: 151952 Hom.: 22175 Cov.: 32 AF XY: 0.502 AC XY: 37276 AN XY: 74270

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.488

Alfa AF: 0.422 Hom.: 22223

Bravo AF: 0.530

Asia WGS AF: 0.365 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs1059823; hg19: chr2-219259844; COSMIC: COSV51916079; COSMIC: COSV51916079;