1-205793011-T-G

Variant names:

• chr1-205793011-T-G
• rs708726
• NM_173854.6:c.1357-1293A>C

Variant summary

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

The NM_173854.6(SLC41A1):​c.1357-1293A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,844 control chromosomes in the GnomAD database, including 31,659 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 0.62 (31659 hom., cov: 30)
• Consequence: SLC41A1 NM_173854.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516
• Publications: 21 publications found

Genes affected

SLC41A1 (HGNC:19429): (solute carrier family 41 member 1) Enables magnesium ion transmembrane transporter activity and magnesium:sodium antiporter activity. Involved in cellular magnesium ion homeostasis; cellular response to magnesium ion; and magnesium ion transmembrane transport. Located in basolateral plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

SLC41A1 Gene-Disease associations (from GenCC):

• kidney disorder

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• nephronophthisis-like nephropathy 2

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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 (NFE) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC41A1	NM_173854.6	c.1357-1293A>C		intron_variant	Intron 10 of 10	ENST00000367137.4	NP_776253.3
SLC41A1	XM_047416887.1	c.1357-1293A>C		intron_variant	Intron 9 of 9		XP_047272843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC41A1	ENST00000367137.4	c.1357-1293A>C		intron_variant	Intron 10 of 10	1	NM_173854.6	ENSP00000356105.3
SLC41A1	ENST00000468057.5	n.1153-1293A>C		intron_variant	Intron 9 of 9	2
SLC41A1	ENST00000484228.1	n.1423-1293A>C		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94407 AN: 151726 Hom.: 31656 Cov.: 30

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.654

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.622 AC: 94438 AN: 151844 Hom.: 31659 Cov.: 30 AF XY: 0.621 AC XY: 46066 AN XY: 74186

African (AFR) AF: 0.377 AC: 15595 AN: 41410

American (AMR) AF: 0.551 AC: 8411 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2594 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2797 AN: 5154

South Asian (SAS) AF: 0.610 AC: 2933 AN: 4806

European-Finnish (FIN) AF: 0.795 AC: 8370 AN: 10526

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51463 AN: 67906

Other (OTH) AF: 0.657 AC: 1384 AN: 2106

Alfa AF: 0.705 Hom.: 66755

Bravo AF: 0.590

Asia WGS AF: 0.562 AC: 1958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.8
DANN	Benign	0.49
PhyloP100		0.52
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: rs708726; hg19: chr1-205762139;