chr1-205808652-G-A

Variant names:

• chr1-205808652-G-A
• rs708730
• NM_173854.6:c.372+1418C>T

Variant summary

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

The NM_173854.6(SLC41A1):​c.372+1418C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,156 control chromosomes in the GnomAD database, including 38,089 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 0.66 (38089 hom., cov: 32)
• Consequence: SLC41A1 NM_173854.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC41A1	NM_173854.6	c.372+1418C>T		intron_variant	Intron 2 of 10	ENST00000367137.4	NP_776253.3
SLC41A1	XM_047416887.1	c.372+1418C>T		intron_variant	Intron 1 of 9		XP_047272843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC41A1	ENST00000367137.4	c.372+1418C>T		intron_variant	Intron 2 of 10	1	NM_173854.6	ENSP00000356105.3

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100878 AN: 152038 Hom.: 38088 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.663 AC: 100898 AN: 152156 Hom.: 38089 Cov.: 32 AF XY: 0.667 AC XY: 49572 AN XY: 74376

African (AFR) AF: 0.272 AC: 11265 AN: 41474

American (AMR) AF: 0.745 AC: 11398 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2645 AN: 3472

East Asian (EAS) AF: 0.785 AC: 4069 AN: 5182

South Asian (SAS) AF: 0.757 AC: 3651 AN: 4826

European-Finnish (FIN) AF: 0.829 AC: 8788 AN: 10598

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.832 AC: 56570 AN: 67992

Other (OTH) AF: 0.705 AC: 1491 AN: 2114

Alfa AF: 0.781 Hom.: 209655

Bravo AF: 0.639

Asia WGS AF: 0.733 AC: 2549 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	0.42
DANN	Benign	0.50
PhyloP100		-0.48
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: rs708730; hg19: chr1-205777780;