1-205795512-G-A

Variant names:

• chr1-205795512-G-A
• rs823156
• NM_173854.6:c.1073-34C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173854.6(SLC41A1):​c.1073-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,612,772 control chromosomes in the GnomAD database, including 517,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (40181 hom., cov: 32)
  • Exomes 𝑓: 0.80 (477036 hom.)
• Consequence: SLC41A1 NM_173854.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.24
• Publications: 60 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-205795512-G-A is Benign according to our data. Variant chr1-205795512-G-A is described in ClinVar as Benign. ClinVar VariationId is 1183197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173854.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A1	NM_173854.6	MANE Select	c.1073-34C>T		intron	N/A	NP_776253.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC41A1	ENST00000367137.4	TSL:1 MANE Select	c.1073-34C>T		intron	N/A	ENSP00000356105.3
	SLC41A1	ENST00000484228.1	TSL:2	n.1105C>T		non_coding_transcript_exon	Exon 1 of 3
	SLC41A1	ENST00000468057.5	TSL:2	n.869-34C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.704 AC: 107067 AN: 152014 Hom.: 40164 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.833

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.724

GnomAD2 exomes AF: 0.772 AC: 192566 AN: 249422 AF XY: 0.778

Gnomad AFR exome AF: 0.409

Gnomad AMR exome AF: 0.743

Gnomad ASJ exome AF: 0.794

Gnomad EAS exome AF: 0.801

Gnomad FIN exome AF: 0.826

Gnomad NFE exome AF: 0.824

Gnomad OTH exome AF: 0.780

GnomAD4 exome AF: 0.805 AC: 1175736 AN: 1460640 Hom.: 477036 Cov.: 46 AF XY: 0.804 AC XY: 584429 AN XY: 726648

African (AFR) AF: 0.400 AC: 13387 AN: 33454

American (AMR) AF: 0.745 AC: 33173 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 20723 AN: 26124

East Asian (EAS) AF: 0.820 AC: 32524 AN: 39670

South Asian (SAS) AF: 0.742 AC: 63932 AN: 86182

European-Finnish (FIN) AF: 0.828 AC: 44160 AN: 53348

Middle Eastern (MID) AF: 0.754 AC: 4346 AN: 5766

European-Non Finnish (NFE) AF: 0.825 AC: 916501 AN: 1111234

Other (OTH) AF: 0.779 AC: 46990 AN: 60344

GnomAD4 genome AF: 0.704 AC: 107128 AN: 152132 Hom.: 40181 Cov.: 32 AF XY: 0.706 AC XY: 52511 AN XY: 74386

African (AFR) AF: 0.421 AC: 17437 AN: 41446

American (AMR) AF: 0.761 AC: 11627 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2692 AN: 3468

East Asian (EAS) AF: 0.792 AC: 4107 AN: 5188

South Asian (SAS) AF: 0.745 AC: 3596 AN: 4826

European-Finnish (FIN) AF: 0.833 AC: 8833 AN: 10602

Middle Eastern (MID) AF: 0.729 AC: 213 AN: 292

European-Non Finnish (NFE) AF: 0.827 AC: 56254 AN: 68000

Other (OTH) AF: 0.727 AC: 1535 AN: 2110

Alfa AF: 0.781 Hom.: 172160

Bravo AF: 0.685

Asia WGS AF: 0.746 AC: 2594 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.46
DANN	Benign	0.46
PhyloP100		-2.2
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: rs823156; hg19: chr1-205764640; COSMIC: COSV65650550;