chr2-218390119-T-C

Position:

• chr2-218390119-T-C

Variant summary

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

The NM_000578.4(SLC11A1):​c.954+91T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,341,436 control chromosomes in the GnomAD database, including 48,279 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 0.25 (4979 hom., cov: 31)
  • Exomes 𝑓: 0.26 (43300 hom.)
• Consequence: SLC11A1 NM_000578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC11A1	NM_000578.4	c.954+91T>C		intron_variant		ENST00000233202.11	NP_000569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11	c.954+91T>C		intron_variant		1	NM_000578.4	ENSP00000233202.6

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38164 AN: 151908 Hom.: 4975 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.265 AC: 314956 AN: 1189410 Hom.: 43300 AF XY: 0.261 AC XY: 153799 AN XY: 589572

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.260

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.251 AC: 38191 AN: 152026 Hom.: 4979 Cov.: 31 AF XY: 0.249 AC XY: 18470 AN XY: 74298

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.274

Alfa AF: 0.260 Hom.: 2907

Bravo AF: 0.257

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.49

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: rs3816560; hg19: chr2-219254842; COSMIC: COSV51916725; COSMIC: COSV51916725;