12-9760134-C-T

Variant names:

• chr12-9760134-C-T
• rs3176789
• NM_001781.2:c.64+623G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001781.2(CD69):​c.64+623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,572 control chromosomes in the GnomAD database, including 5,317 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5317 hom., cov: 31)
• Consequence: CD69 NM_001781.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

Genes affected

CD69 (HGNC:1694): (CD69 molecule) This gene encodes a member of the calcium dependent lectin superfamily of type II transmembrane receptors. Expression of the encoded protein is induced upon activation of T lymphocytes, and may play a role in proliferation. Furthermore, the protein may act to transmit signals in natural killer cells and platelets. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD69	NM_001781.2	c.64+623G>A		intron_variant	Intron 1 of 4	ENST00000228434.7	NP_001772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD69	ENST00000228434.7	c.64+623G>A		intron_variant	Intron 1 of 4	1	NM_001781.2	ENSP00000228434.3
CD69	ENST00000536709.1	c.64+623G>A		intron_variant	Intron 1 of 3	2		ENSP00000442597.1
CD69	ENST00000416624.6	n.145+623G>A		intron_variant	Intron 1 of 2	2
CD69	ENST00000543147.1	n.145+623G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37420 AN: 151454 Hom.: 5302 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.256

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37449 AN: 151572 Hom.: 5317 Cov.: 31 AF XY: 0.251 AC XY: 18564 AN XY: 74016

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.264

Alfa AF: 0.259 Hom.: 707

Bravo AF: 0.254

Asia WGS AF: 0.401 AC: 1392 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs3176789; hg19: chr12-9912730;