rs2233915

Variant names:

• chr9-113256221-C-G
• rs2233915
• NM_001859.4:c.73C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-113256221-C-G
• chr9-113256221-C-T

Variant summary

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

The NM_001859.4(SLC31A1):​c.73C>G​(p.Pro25Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,613,598 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P25L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.022 (129 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (119 hom.)
• Consequence: SLC31A1 NM_001859.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.314
• Publications: 7 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]

CDC26 (HGNC:17839): (cell division cycle 26) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc26, a component of cell cycle anaphase-promoting complex (APC). APC is composed of a group of highly conserved proteins and functions as a cell cycle-regulated ubiquitin-protein ligase. APC thus is responsible for the cell cycle regulated proteolysis of various proteins. [provided by RefSeq, Jul 2008]

LOC107987119 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014228523).
• BP6: Variant 9-113256221-C-G is Benign according to our data. Variant chr9-113256221-C-G is described in ClinVar as Benign. ClinVar VariationId is 713723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001859.4. 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
	SLC31A1	NM_001859.4	MANE Select	c.73C>G	p.Pro25Ala	missense	Exon 2 of 5	NP_001850.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC31A1	ENST00000374212.5	TSL:1 MANE Select	c.73C>G	p.Pro25Ala	missense	Exon 2 of 5	ENSP00000363329.4
	CDC26	ENST00000490408.5	TSL:3	n.495-178G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3301 AN: 152088 Hom.: 129 Cov.: 32

Gnomad AFR AF: 0.0764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00581 AC: 1460 AN: 251262 AF XY: 0.00440

Gnomad AFR exome AF: 0.0796

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00228 AC: 3332 AN: 1461392 Hom.: 119 Cov.: 31 AF XY: 0.00192 AC XY: 1398 AN XY: 726996

African (AFR) AF: 0.0796 AC: 2665 AN: 33460

American (AMR) AF: 0.00407 AC: 182 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00148 AC: 8 AN: 5390

European-Non Finnish (NFE) AF: 0.000149 AC: 166 AN: 1111992

Other (OTH) AF: 0.00464 AC: 280 AN: 60348

GnomAD4 genome AF: 0.0217 AC: 3303 AN: 152206 Hom.: 129 Cov.: 32 AF XY: 0.0210 AC XY: 1562 AN XY: 74428

African (AFR) AF: 0.0762 AC: 3161 AN: 41484

American (AMR) AF: 0.00582 AC: 89 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68028

Other (OTH) AF: 0.0133 AC: 28 AN: 2108

Alfa AF: 0.00684 Hom.: 9

Bravo AF: 0.0246

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0751 AC: 331

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00725 AC: 880

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.6
DANN	Benign	0.85
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.31
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.063
Sift	Benign	0.73	T
Sift4G	Benign	0.85	T
Polyphen		0.018	B
Vest4		0.19
MVP		0.38
MPC		0.47
ClinPred		0.0076	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.54
Mutation Taster		=97/3	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: rs2233915; hg19: chr9-116018501;