5-75666988-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BS1 BS2

The NM_001276713.2(ANKDD1B):c.1388G>A(p.Trp463Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.000747 in 1,474,794 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (8 hom.)
• Consequence: ANKDD1B NM_001276713.2 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.69

Genes affected

ANKDD1B (HGNC:32525): (ankyrin repeat and death domain containing 1B) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PM4: Stoplost variant in NM_001276713.2 Downstream stopcodon found after 588 codons.
• BP6: Variant 5-75666988-G-A is Benign according to our data. Variant chr5-75666988-G-A is described in ClinVar as [Benign]. Clinvar id is 718612.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00109 (166/152274) while in subpopulation EAS AF= 0.0282 (146/5170). AF 95% confidence interval is 0.0245. There are 1 homozygotes in gnomad4. There are 92 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKDD1B	NM_001276713.2	c.1388G>A	p.Trp463Ter	stop_gained	12/14	ENST00000601380.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKDD1B	ENST00000601380.4	c.1388G>A	p.Trp463Ter	stop_gained	12/14	5	NM_001276713.2	P1

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 166 AN: 152158 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0282

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00354 AC: 285 AN: 80578 Hom.: 3 AF XY: 0.00348 AC XY: 144 AN XY: 41356

Gnomad AFR exome AF: 0.000345

Gnomad AMR exome AF: 0.000193

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0291

Gnomad SAS exome AF: 0.000951

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000316

Gnomad OTH exome AF: 0.00154

GnomAD4 exome AF: 0.000707 AC: 935 AN: 1322520 Hom.: 8 Cov.: 30 AF XY: 0.000694 AC XY: 449 AN XY: 646694

Gnomad4 AFR exome AF: 0.000135

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0202

Gnomad4 SAS exome AF: 0.000897

Gnomad4 FIN exome AF: 0.0000319

Gnomad4 NFE exome AF: 0.0000219

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152274 Hom.: 1 Cov.: 32 AF XY: 0.00124 AC XY: 92 AN XY: 74442

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0282

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000425 Hom.: 0

Bravo AF: 0.00118

ExAC AF: 0.000467 AC: 9

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Pathogenic	0.60
Cadd	Pathogenic	38
Dann	Benign	0.78
FATHMM_MKL	Uncertain	0.93	D
Vest4		0.17
GERP RS		5.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs77253171; hg19: chr5-74962813;