21-43805987-A-G

Variant names:

• chr21-43805987-A-G
• rs6518322
• ENST00000437258.5:n.703T>C

Variant summary

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

The ENST00000437258.5(AATBC):​n.703T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,958 control chromosomes in the GnomAD database, including 26,971 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 0.57 (26960 hom., cov: 31)
  • Exomes 𝑓: 0.56 (11 hom.)
• Consequence: AATBC ENST00000437258.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 9 publications found

Genes affected

AATBC (HGNC:51526): (apoptosis associated transcript in bladder cancer)

RRP1 (HGNC:18785): (ribosomal RNA processing 1) The protein encoded by this gene is the putative homolog of the yeast ribosomal RNA processing protein RRP1. The encoded protein is involved in the late stages of nucleologenesis at the end of mitosis, and may be required for the generation of 28S rRNA. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000437258.5. 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
	AATBC	NR_026961.1		n.4369T>C		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AATBC	ENST00000437258.5	TSL:1	n.703T>C		non_coding_transcript_exon	Exon 2 of 2
	AATBC	ENST00000400385.2	TSL:2	n.4369T>C		non_coding_transcript_exon	Exon 2 of 2
	AATBC	ENST00000448247.5	TSL:2	n.1660T>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86953 AN: 151768 Hom.: 26914 Cov.: 31

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.556 AC: 40 AN: 72 Hom.: 11 Cov.: 0 AF XY: 0.500 AC XY: 14 AN XY: 28

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) AF: 0.603 AC: 35 AN: 58

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 5 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.573 AC: 87056 AN: 151886 Hom.: 26960 Cov.: 31 AF XY: 0.580 AC XY: 43040 AN XY: 74242

African (AFR) AF: 0.777 AC: 32162 AN: 41410

American (AMR) AF: 0.641 AC: 9791 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3468

East Asian (EAS) AF: 0.771 AC: 3976 AN: 5160

South Asian (SAS) AF: 0.727 AC: 3489 AN: 4796

European-Finnish (FIN) AF: 0.464 AC: 4895 AN: 10552

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29167 AN: 67924

Other (OTH) AF: 0.565 AC: 1192 AN: 2108

Alfa AF: 0.533 Hom.: 4099

Bravo AF: 0.595

Asia WGS AF: 0.751 AC: 2612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs6518322; hg19: chr21-45225868;