ENST00000004531.14:c.102G>A

Variant names:

• chr8-17543321-G-A
• rs114541623
• ENST00000004531.14:c.102G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The ENST00000004531.14(SLC7A2):​c.102G>A​(p.Ser34Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,599,716 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.010 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (28 hom.)
• Consequence: SLC7A2 ENST00000004531.14 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0500
• Publications: 1 publications found

Genes affected

SLC7A2 (HGNC:11060): (solute carrier family 7 member 2) The protein encoded by this gene is a cationic amino acid transporter and a member of the APC (amino acid-polyamine-organocation) family of transporters. The encoded membrane protein is responsible for the cellular uptake of arginine, lysine and ornithine. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 8-17543321-G-A is Benign according to our data. Variant chr8-17543321-G-A is described in ClinVar as Benign. ClinVar VariationId is 3039705.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1561/152200) while in subpopulation AFR AF = 0.0354 (1469/41516). AF 95% confidence interval is 0.0339. There are 20 homozygotes in GnomAd4. There are 742 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000004531.14. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A2	NM_001370338.1	MANE Select	c.-19G>A		5_prime_UTR	Exon 3 of 13	NP_001357267.1	P52569-1
	SLC7A2	NM_001164771.2		c.102G>A	p.Ser34Ser	synonymous	Exon 2 of 12	NP_001158243.1	P52569-3
	SLC7A2	NM_003046.6		c.102G>A	p.Ser34Ser	synonymous	Exon 2 of 12	NP_003037.4	P52569-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A2	ENST00000004531.14	TSL:1	c.102G>A	p.Ser34Ser	synonymous	Exon 2 of 12	ENSP00000004531.10	P52569-3
	SLC7A2	ENST00000398090.3	TSL:1	c.102G>A	p.Ser34Ser	synonymous	Exon 2 of 12	ENSP00000381164.3	P52569-2
	SLC7A2	ENST00000494857.6	TSL:5 MANE Select	c.-19G>A		5_prime_UTR	Exon 3 of 13	ENSP00000419140.2	P52569-1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1561 AN: 152082 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00717

GnomAD2 exomes AF: 0.00282 AC: 672 AN: 238526 AF XY: 0.00202

Gnomad AFR exome AF: 0.0369

Gnomad AMR exome AF: 0.00175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000102

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.00107 AC: 1546 AN: 1447516 Hom.: 28 Cov.: 32 AF XY: 0.000931 AC XY: 669 AN XY: 718806

African (AFR) AF: 0.0363 AC: 1198 AN: 33036

American (AMR) AF: 0.00166 AC: 71 AN: 42682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24892

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39588

South Asian (SAS) AF: 0.000359 AC: 30 AN: 83664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53016

Middle Eastern (MID) AF: 0.00141 AC: 8 AN: 5676

European-Non Finnish (NFE) AF: 0.0000923 AC: 102 AN: 1105190

Other (OTH) AF: 0.00223 AC: 133 AN: 59772

GnomAD4 genome AF: 0.0103 AC: 1561 AN: 152200 Hom.: 20 Cov.: 32 AF XY: 0.00997 AC XY: 742 AN XY: 74402

African (AFR) AF: 0.0354 AC: 1469 AN: 41516

American (AMR) AF: 0.00431 AC: 66 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68008

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00608 Hom.: 9

Bravo AF: 0.0115

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC7A2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.6
DANN	Benign	0.61
PhyloP100		0.050
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=298/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs114541623; hg19: chr8-17400830;