21-27448105-T-G

Variant names:

• chr21-27448105-T-G
• rs239627
• ENST00000420186.2:n.202+273A>C

Variant summary

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

The ENST00000420186.2(ENSG00000231236):​n.202+273A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,060 control chromosomes in the GnomAD database, including 54,018 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 0.84 (54018 hom., cov: 30)
• Consequence: ENSG00000231236 ENST00000420186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 1 publications found

Genes affected

ENSG00000231236 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372762	XR_001754990.2	n.263+273A>C		intron_variant	Intron 1 of 1
LOC105372762	XR_007067830.1	n.263+273A>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000231236	ENST00000420186.2	n.202+273A>C		intron_variant	Intron 1 of 3	1
ENSG00000231236	ENST00000764472.1	n.252+273A>C		intron_variant	Intron 1 of 5
ENSG00000231236	ENST00000764473.1	n.234+273A>C		intron_variant	Intron 1 of 2
ENSG00000231236	ENST00000764474.1	n.263+273A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127946 AN: 151942 Hom.: 53987 Cov.: 30

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.842 AC: 128036 AN: 152060 Hom.: 54018 Cov.: 30 AF XY: 0.843 AC XY: 62612 AN XY: 74310

African (AFR) AF: 0.859 AC: 35645 AN: 41472

American (AMR) AF: 0.801 AC: 12222 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2798 AN: 3472

East Asian (EAS) AF: 0.739 AC: 3792 AN: 5132

South Asian (SAS) AF: 0.783 AC: 3764 AN: 4810

European-Finnish (FIN) AF: 0.908 AC: 9621 AN: 10600

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57482 AN: 67992

Other (OTH) AF: 0.816 AC: 1723 AN: 2112

Alfa AF: 0.846 Hom.: 4389

Bravo AF: 0.835

Asia WGS AF: 0.741 AC: 2577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.74
PhyloP100		0.080

Splicing

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

Other links and lift over

dbSNP: rs239627; hg19: chr21-28820424;