rs143114570

Variant names:

• chr19-51225219-G-A
• rs143114570
• NM_001772.4:c.39G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001772.4(CD33):​c.39G>A​(p.Gly13Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000803 in 1,613,328 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G13G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0042 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (6 hom.)
• Consequence: CD33 NM_001772.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00006033
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.926
• Publications: 0 publications found

Genes affected

CD33 (HGNC:1659): (CD33 molecule) Enables protein phosphatase binding activity and sialic acid binding activity. Involved in several processes, including negative regulation of cytokine production; negative regulation of monocyte activation; and positive regulation of protein tyrosine phosphatase activity. Located in several cellular components, including Golgi apparatus; external side of plasma membrane; and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268595 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-51225219-G-A is Benign according to our data. Variant chr19-51225219-G-A is described in ClinVar as Benign. ClinVar VariationId is 717093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.926 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000446 (651/1461012) while in subpopulation AFR AF = 0.0163 (547/33462). AF 95% confidence interval is 0.0152. There are 6 homozygotes in GnomAdExome4. There are 262 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001772.4. 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
	CD33	NM_001772.4	MANE Select	c.39G>A	p.Gly13Gly	splice_region synonymous	Exon 2 of 7	NP_001763.3	Q546G0
	CD33	NM_001177608.2		c.39G>A	p.Gly13Gly	splice_region synonymous	Exon 2 of 7	NP_001171079.1	P20138-2
	CD33	NM_001082618.2		c.37+64G>A		intron	N/A	NP_001076087.1	P20138-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD33	ENST00000262262.5	TSL:1 MANE Select	c.39G>A	p.Gly13Gly	splice_region synonymous	Exon 2 of 7	ENSP00000262262.3	P20138-1
	CD33	ENST00000391796.7	TSL:1	c.39G>A	p.Gly13Gly	splice_region synonymous	Exon 2 of 7	ENSP00000375673.2	P20138-2
	CD33	ENST00000421133.6	TSL:1	c.37+64G>A		intron	N/A	ENSP00000410126.1	P20138-3

Frequencies

GnomAD3 genomes AF: 0.00419 AC: 638 AN: 152198 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

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: 0.00

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00110 AC: 276 AN: 250394 AF XY: 0.000850

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.000724

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000446 AC: 651 AN: 1461012 Hom.: 6 Cov.: 31 AF XY: 0.000361 AC XY: 262 AN XY: 726754

African (AFR) AF: 0.0163 AC: 547 AN: 33462

American (AMR) AF: 0.000671 AC: 30 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86216

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53278

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5764

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111486

Other (OTH) AF: 0.000729 AC: 44 AN: 60350

GnomAD4 genome AF: 0.00423 AC: 644 AN: 152316 Hom.: 6 Cov.: 32 AF XY: 0.00416 AC XY: 310 AN XY: 74478

African (AFR) AF: 0.0148 AC: 616 AN: 41574

American (AMR) AF: 0.00131 AC: 20 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

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

Alfa AF: 0.00163 Hom.: 0

Bravo AF: 0.00468

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.75
PhyloP100		-0.93
PromoterAI		-0.059	Neutral
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000060
dbscSNV1_RF	Benign	0.0020
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: rs143114570; hg19: chr19-51728475;