21-27362678-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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124905003	XR_007067831.1	n.1855G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000231236	ENST00000420186.2	n.332-1522G>A		intron_variant	Intron 3 of 3	1
ENSG00000236332	ENST00000447384.1	n.291-35C>T		intron_variant	Intron 1 of 4	1
ENSG00000236332	ENST00000656258.2	n.334-35C>T		intron_variant	Intron 1 of 3

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 v4.3

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;