9-113241753-C-A

Variant names:

• chr9-113241753-C-A
• rs12686377
• NM_001859.4:c.-35-14361C>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.-35-14361C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,144 control chromosomes in the GnomAD database, including 1,951 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 0.15 (1951 hom., cov: 32)
• Consequence: SLC31A1 NM_001859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 22 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC31A1	NM_001859.4	c.-35-14361C>A		intron_variant	Intron 1 of 4	ENST00000374212.5	NP_001850.1
LOC107987119	XR_007061736.1	n.397-1G>T		splice_acceptor_variant, intron_variant	Intron 1 of 1
LOC107987119	XR_007061737.1	n.272-1G>T		splice_acceptor_variant, intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC31A1	ENST00000374212.5	c.-35-14361C>A		intron_variant	Intron 1 of 4	1	NM_001859.4	ENSP00000363329.4

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22444 AN: 152026 Hom.: 1949 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.148 AC: 22459 AN: 152144 Hom.: 1951 Cov.: 32 AF XY: 0.152 AC XY: 11295 AN XY: 74378

African (AFR) AF: 0.182 AC: 7559 AN: 41492

American (AMR) AF: 0.108 AC: 1650 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1750 AN: 5168

South Asian (SAS) AF: 0.255 AC: 1231 AN: 4826

European-Finnish (FIN) AF: 0.142 AC: 1504 AN: 10570

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7557 AN: 68010

Other (OTH) AF: 0.159 AC: 337 AN: 2116

Alfa AF: 0.109 Hom.: 482

Bravo AF: 0.148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.7
DANN	Benign	0.70
PhyloP100		0.19
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: rs12686377; hg19: chr9-116004033;