rs6477998

Variant names:

• chr9-113234969-C-A
• rs6477998
• NM_001859.4:c.-36+13291C>A

Variant summary

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

The NM_001859.4(SLC31A1):​c.-36+13291C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,822 control chromosomes in the GnomAD database, including 17,187 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 0.47 (17187 hom., cov: 32)
• Consequence: SLC31A1 NM_001859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• Publications: 15 publications found

Genes affected

SLC31A1 (HGNC:11016): (solute carrier family 31 member 1) The protein encoded by this gene is a high-affinity copper transporter found in the cell membrane. The encoded protein functions as a homotrimer to effect the uptake of dietary copper. [provided by RefSeq, Aug 2011]

SLC31A1 Gene-Disease associations (from GenCC):

• neurodegeneration and seizures due to copper transport defect

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

LOC107987119 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC31A1	NM_001859.4	c.-36+13291C>A		intron_variant	Intron 1 of 4	ENST00000374212.5	NP_001850.1
LOC107987119	XR_007061736.1	n.7180G>T		non_coding_transcript_exon_variant	Exon 2 of 2
LOC107987119	XR_007061737.1	n.7055G>T		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC31A1	ENST00000374212.5	c.-36+13291C>A		intron_variant	Intron 1 of 4	1	NM_001859.4	ENSP00000363329.4

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71506 AN: 151704 Hom.: 17171 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.471 AC: 71576 AN: 151822 Hom.: 17187 Cov.: 32 AF XY: 0.475 AC XY: 35263 AN XY: 74196

African (AFR) AF: 0.535 AC: 22130 AN: 41402

American (AMR) AF: 0.416 AC: 6349 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1829 AN: 3468

East Asian (EAS) AF: 0.481 AC: 2479 AN: 5158

South Asian (SAS) AF: 0.589 AC: 2839 AN: 4816

European-Finnish (FIN) AF: 0.475 AC: 4997 AN: 10510

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29433 AN: 67914

Other (OTH) AF: 0.450 AC: 949 AN: 2110

Alfa AF: 0.449 Hom.: 46879

Bravo AF: 0.471

Asia WGS AF: 0.566 AC: 1962 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.49
DANN	Benign	0.61
PhyloP100		-0.67
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: rs6477998; hg19: chr9-115997249; COSMIC: COSV65264737;