ENST00000430064.1:n.276-98G>C

Variant names:

• chr21-16863074-C-G
• rs415277
• ENST00000430064.1:n.276-98G>C

Variant summary

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

The ENST00000430064.1(ENSG00000232886):​n.276-98G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 151,986 control chromosomes in the GnomAD database, including 67,529 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 0.94 (67520 hom., cov: 30)
  • Exomes 𝑓: 0.95 (9 hom.)
• Consequence: ENSG00000232886 ENST00000430064.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.801
• Publications: 1 publications found

Genes affected

ENSG00000232886 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000430064.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000232886	ENST00000430064.1	TSL:3	n.276-98G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142447 AN: 151848 Hom.: 67490 Cov.: 30

Gnomad AFR AF: 0.786

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.954

GnomAD4 exome AF: 0.950 AC: 19 AN: 20 Hom.: 9 AF XY: 1.00 AC XY: 18 AN XY: 18

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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) AC: 0 AN: 0

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 18 AN: 18

Other (OTH) AF: 0.500 AC: 1 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.938 AC: 142526 AN: 151966 Hom.: 67520 Cov.: 30 AF XY: 0.939 AC XY: 69773 AN XY: 74282

African (AFR) AF: 0.786 AC: 32544 AN: 41410

American (AMR) AF: 0.975 AC: 14848 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3461 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5140 AN: 5140

South Asian (SAS) AF: 0.999 AC: 4825 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10604 AN: 10604

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67884 AN: 67952

Other (OTH) AF: 0.954 AC: 2019 AN: 2116

Alfa AF: 0.965 Hom.: 8846

Bravo AF: 0.930

Asia WGS AF: 0.984 AC: 3422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.1
DANN	Benign	0.60
PhyloP100		0.80

Splicing

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

Other links and lift over

dbSNP: rs415277; hg19: chr21-18235394;