5-139372262-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005847.5(SLC23A1):c.1550-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,607,672 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (31 hom.)
• Consequence: SLC23A1 NM_005847.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003133
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.20

Genes affected

SLC23A1 (HGNC:10974): (solute carrier family 23 member 1) The absorption of vitamin C into the body and its distribution to organs requires two sodium-dependent vitamin C transporters. This gene encodes one of the two transporters. The encoded protein is active in bulk vitamin C transport involving epithelial surfaces. Previously, this gene had an official symbol of SLC23A2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 5-139372262-G-A is Benign according to our data. Variant chr5-139372262-G-A is described in ClinVar as [Benign]. Clinvar id is 785138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1733/152296) while in subpopulation AFR AF= 0.0389 (1616/41556). AF 95% confidence interval is 0.0373. There are 23 homozygotes in gnomad4. There are 776 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC23A1	NM_005847.5	c.1550-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000348729.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC23A1	ENST00000348729.8	c.1550-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005847.5	P1
SLC23A1	ENST00000353963.7	c.1562-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1732 AN: 152178 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00334 AC: 831 AN: 248644 Hom.: 15 AF XY: 0.00228 AC XY: 308 AN XY: 134874

Gnomad AFR exome AF: 0.0439

Gnomad AMR exome AF: 0.00292

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000266

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00137 AC: 1997 AN: 1455376 Hom.: 31 Cov.: 31 AF XY: 0.00119 AC XY: 857 AN XY: 723128

Gnomad4 AFR exome AF: 0.0432

Gnomad4 AMR exome AF: 0.00336

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000929

Gnomad4 FIN exome AF: 0.0000377

Gnomad4 NFE exome AF: 0.000187

Gnomad4 OTH exome AF: 0.00292

GnomAD4 genome AF: 0.0114 AC: 1733 AN: 152296 Hom.: 23 Cov.: 32 AF XY: 0.0104 AC XY: 776 AN XY: 74466

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00572 Hom.: 7

Bravo AF: 0.0130

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	10
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.0040
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

Publications

LitVar

Other links and lift over

dbSNP: rs116767990; hg19: chr5-138707951;