rs113496485

Variant names:

• chr20-46733738-G-A
• rs113496485
• NM_030777.4:c.1548-18G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030777.4(SLC2A10):​c.1548-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,611,506 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (19 hom.)
• Consequence: SLC2A10 NM_030777.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.08
• Publications: 2 publications found

Genes affected

SLC2A10 (HGNC:13444): (solute carrier family 2 member 10) This gene encodes a member of the class III facilitative glucose transporter family. The encoded protein plays a role in regulation of glucose homeostasis. Mutations in this gene have been associated with arterial tortuosity syndrome.[provided by RefSeq, Dec 2009]

SLC2A10 Gene-Disease associations (from GenCC):

• arterial tortuosity syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 20-46733738-G-A is Benign according to our data. Variant chr20-46733738-G-A is described in ClinVar as Benign. ClinVar VariationId is 139180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00691 (1052/152280) while in subpopulation AFR AF = 0.024 (996/41550). AF 95% confidence interval is 0.0227. There are 11 homozygotes in GnomAd4. There are 493 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030777.4. 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
	SLC2A10	NM_030777.4	MANE Select	c.1548-18G>A		intron	N/A	NP_110404.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A10	ENST00000359271.4	TSL:1 MANE Select	c.1548-18G>A		intron	N/A	ENSP00000352216.2
	SLC2A10	ENST00000862794.1		c.1842-18G>A		intron	N/A	ENSP00000532853.1
	SLC2A10	ENST00000862792.1		c.1680-18G>A		intron	N/A	ENSP00000532851.1

Frequencies

GnomAD3 genomes AF: 0.00675 AC: 1027 AN: 152162 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00192 AC: 480 AN: 250304 AF XY: 0.00139

Gnomad AFR exome AF: 0.0258

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000709

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000790 AC: 1153 AN: 1459226 Hom.: 19 Cov.: 30 AF XY: 0.000678 AC XY: 492 AN XY: 726046

African (AFR) AF: 0.0263 AC: 880 AN: 33406

American (AMR) AF: 0.00134 AC: 60 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53134

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5762

European-Non Finnish (NFE) AF: 0.0000523 AC: 58 AN: 1109854

Other (OTH) AF: 0.00220 AC: 133 AN: 60324

GnomAD4 genome AF: 0.00691 AC: 1052 AN: 152280 Hom.: 11 Cov.: 32 AF XY: 0.00662 AC XY: 493 AN XY: 74458

African (AFR) AF: 0.0240 AC: 996 AN: 41550

American (AMR) AF: 0.00222 AC: 34 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68014

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00467 Hom.: 1

Bravo AF: 0.00765

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Arterial tortuosity syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0080
DANN	Benign	0.55
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs113496485; hg19: chr20-45362377;