NM_000578.4:c.954+91T>C

Variant names:

• chr2-218390119-T-C
• rs3816560
• NM_000578.4:c.954+91T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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
• Mycobacterium tuberculosis, susceptibility

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	NM_000578.4	MANE Select	c.954+91T>C		intron	N/A	NP_000569.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	ENST00000233202.11	TSL:1 MANE Select	c.954+91T>C		intron	N/A	ENSP00000233202.6	P49279-1
	SLC11A1	ENST00000354352.9	TSL:1	n.*536+91T>C		intron	N/A	ENSP00000346320.5	Q9HBK0
	SLC11A1	ENST00000468221.5	TSL:1	n.3215+91T>C		intron	N/A

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

African (AFR) AF: 0.226 AC: 6016 AN: 26660

American (AMR) AF: 0.308 AC: 7940 AN: 25752

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 4803 AN: 18650

East Asian (EAS) AF: 0.135 AC: 5052 AN: 37502

South Asian (SAS) AF: 0.136 AC: 8875 AN: 65374

European-Finnish (FIN) AF: 0.260 AC: 12601 AN: 48454

Middle Eastern (MID) AF: 0.269 AC: 1062 AN: 3952

European-Non Finnish (NFE) AF: 0.280 AC: 255830 AN: 912944

Other (OTH) AF: 0.255 AC: 12777 AN: 50122

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

African (AFR) AF: 0.222 AC: 9208 AN: 41468

American (AMR) AF: 0.301 AC: 4588 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 903 AN: 3464

East Asian (EAS) AF: 0.127 AC: 657 AN: 5170

South Asian (SAS) AF: 0.136 AC: 657 AN: 4816

European-Finnish (FIN) AF: 0.257 AC: 2718 AN: 10560

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18499 AN: 67966

Other (OTH) AF: 0.274 AC: 579 AN: 2112

Alfa AF: 0.261 Hom.: 3187

Bravo AF: 0.257

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.49
PhyloP100		-0.50
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: rs3816560; hg19: chr2-219254842; COSMIC: COSV51916725; COSMIC: COSV51916725;