12-9760134-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.120 AC: 4969 AN: 41290

American (AMR) AF: 0.339 AC: 5174 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2597 AN: 5170

South Asian (SAS) AF: 0.282 AC: 1356 AN: 4812

European-Finnish (FIN) AF: 0.255 AC: 2659 AN: 10444

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19192 AN: 67846

Other (OTH) AF: 0.264 AC: 551 AN: 2090

Alfa AF: 0.253 Hom.: 715

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
PhyloP100		-0.093
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3176789; hg19: chr12-9912730;