chr9-113224129-T-G

Variant names:

• chr9-113224129-T-G
• rs10981694
• NM_001859.4:c.-36+2451T>G

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+2451T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 152,250 control chromosomes in the GnomAD database, including 838 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 0.090 (838 hom., cov: 32)
• Consequence: SLC31A1 NM_001859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 19 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)

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 (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC31A1	NM_001859.4	c.-36+2451T>G		intron_variant	Intron 1 of 4	ENST00000374212.5	NP_001850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC31A1	ENST00000374212.5	c.-36+2451T>G		intron_variant	Intron 1 of 4	1	NM_001859.4	ENSP00000363329.4
SLC31A1	ENST00000496650.1	n.92+2451T>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13662 AN: 152132 Hom.: 834 Cov.: 32

Gnomad AFR AF: 0.0256

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0971

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

GnomAD4 genome AF: 0.0898 AC: 13672 AN: 152250 Hom.: 838 Cov.: 32 AF XY: 0.0888 AC XY: 6613 AN XY: 74448

African (AFR) AF: 0.0255 AC: 1061 AN: 41556

American (AMR) AF: 0.136 AC: 2077 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3468

East Asian (EAS) AF: 0.238 AC: 1233 AN: 5174

South Asian (SAS) AF: 0.104 AC: 502 AN: 4830

European-Finnish (FIN) AF: 0.0604 AC: 641 AN: 10614

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

European-Non Finnish (NFE) AF: 0.110 AC: 7476 AN: 68002

Other (OTH) AF: 0.0990 AC: 209 AN: 2112

Alfa AF: 0.103 Hom.: 1472

Bravo AF: 0.0952

Asia WGS AF: 0.147 AC: 510 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.1
DANN	Benign	0.66
PhyloP100		1.6
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: rs10981694; hg19: chr9-115986409;