chr21-27362678-C-T

Variant names:

• chr21-27362678-C-T
• rs9977499
• ENST00000420186.2:n.332-1522G>A

Variant summary

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

The ENST00000420186.2(ENSG00000231236):​n.332-1522G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,008 control chromosomes in the GnomAD database, including 18,567 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 0.47 (18567 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000231236 ENST00000420186.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 11 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000420186.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000231236	ENST00000420186.2	TSL:1	n.332-1522G>A		intron	N/A
	ENSG00000236332	ENST00000447384.1	TSL:1	n.291-35C>T		intron	N/A
	ENSG00000236332	ENST00000656258.2		n.334-35C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71079 AN: 151890 Hom.: 18548 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.467

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.468 AC: 71115 AN: 152008 Hom.: 18567 Cov.: 32 AF XY: 0.462 AC XY: 34344 AN XY: 74300

African (AFR) AF: 0.252 AC: 10460 AN: 41458

American (AMR) AF: 0.461 AC: 7024 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1741 AN: 3468

East Asian (EAS) AF: 0.190 AC: 986 AN: 5178

South Asian (SAS) AF: 0.571 AC: 2755 AN: 4822

European-Finnish (FIN) AF: 0.495 AC: 5215 AN: 10538

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41337 AN: 67982

Other (OTH) AF: 0.471 AC: 993 AN: 2110

Alfa AF: 0.536 Hom.: 46106

Bravo AF: 0.448

Asia WGS AF: 0.352 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.56
DANN	Benign	0.78
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs9977499; hg19: chr21-28734997;