ENST00000422876.2:n.340T>C

Variant names:

• chr22-25564140-A-G
• rs41258004
• ENST00000422876.2:n.340T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422876.2(GRK3-AS1):​n.340T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 152,326 control chromosomes in the GnomAD database, including 844 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 0.087 (844 hom., cov: 32)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: GRK3-AS1 ENST00000422876.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 1 publications found

Genes affected

GRK3-AS1 (HGNC:55679): (GRK3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRK3-AS1	NR_183556.1	n.368T>C		non_coding_transcript_exon_variant	Exon 2 of 4
GRK3-AS1	NR_183557.1	n.371T>C		non_coding_transcript_exon_variant	Exon 2 of 4
GRK3-AS1	NR_183558.1	n.371T>C		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRK3-AS1	ENST00000422876.2	n.340T>C		non_coding_transcript_exon_variant	Exon 2 of 3	2
GRK3-AS1	ENST00000453811.2	n.342T>C		non_coding_transcript_exon_variant	Exon 2 of 4	3
GRK3-AS1	ENST00000661676.2	n.623T>C		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13207 AN: 152160 Hom.: 837 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.0872

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0703

GnomAD4 exome AF: 0.0208 AC: 1 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.0250 AC XY: 1 AN XY: 40

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0263 AC: 1 AN: 38

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0869 AC: 13240 AN: 152278 Hom.: 844 Cov.: 32 AF XY: 0.0858 AC XY: 6389 AN XY: 74456

African (AFR) AF: 0.185 AC: 7706 AN: 41554

American (AMR) AF: 0.0484 AC: 740 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3470

East Asian (EAS) AF: 0.0477 AC: 247 AN: 5182

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4820

European-Finnish (FIN) AF: 0.0872 AC: 925 AN: 10612

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0477 AC: 3246 AN: 68018

Other (OTH) AF: 0.0691 AC: 146 AN: 2112

Alfa AF: 0.0708 Hom.: 84

Bravo AF: 0.0875

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.47
DANN	Benign	0.57
PhyloP100		-1.5
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41258004; hg19: chr22-25960107;