ENST00000454622.2:n.201+41263C>G

Variant names:

• chr21-33029641-G-C
• rs9653711
• ENST00000454622.2:n.201+41263C>G

Variant summary

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

The ENST00000454622.2(ENSG00000227757):​n.201+41263C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,112 control chromosomes in the GnomAD database, including 15,431 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 0.41 (15431 hom., cov: 33)
• Consequence: ENSG00000227757 ENST00000454622.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07
• Publications: 10 publications found

Genes affected

ENSG00000227757 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000227757	ENST00000454622.2	n.201+41263C>G		intron_variant	Intron 1 of 1	2
ENSG00000227757	ENST00000777421.1	n.91+41263C>G		intron_variant	Intron 1 of 1
ENSG00000227757	ENST00000777422.1	n.108-6715C>G		intron_variant	Intron 1 of 1
ENSG00000301417	ENST00000778765.1	n.49-70G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63029 AN: 151994 Hom.: 15429 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.414 AC: 63036 AN: 152112 Hom.: 15431 Cov.: 33 AF XY: 0.413 AC XY: 30732 AN XY: 74358

African (AFR) AF: 0.159 AC: 6597 AN: 41500

American (AMR) AF: 0.447 AC: 6831 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2228 AN: 3468

East Asian (EAS) AF: 0.168 AC: 868 AN: 5170

South Asian (SAS) AF: 0.439 AC: 2118 AN: 4826

European-Finnish (FIN) AF: 0.520 AC: 5501 AN: 10574

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37562 AN: 67966

Other (OTH) AF: 0.447 AC: 943 AN: 2110

Alfa AF: 0.335 Hom.: 980

Bravo AF: 0.400

Asia WGS AF: 0.268 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.029
DANN	Benign	0.49
PhyloP100		-3.1

Splicing

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

Other links and lift over

dbSNP: rs9653711; hg19: chr21-34401949; COSMIC: COSV60973281;