5-75611813-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001276713.2(ANKDD1B):c.179C>A(p.Ala60Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,231,902 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (45 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (31 hom.)
• Consequence: ANKDD1B NM_001276713.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003774017).
• BP6: Variant 5-75611813-C-A is Benign according to our data. Variant chr5-75611813-C-A is described in ClinVar as [Benign]. Clinvar id is 774178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0142 (2160/152250) while in subpopulation AFR AF= 0.0479 (1992/41552). AF 95% confidence interval is 0.0462. There are 45 homozygotes in gnomad4. There are 1033 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKDD1B	NM_001276713.2	c.179C>A	p.Ala60Asp	missense_variant	1/14	ENST00000601380.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKDD1B	ENST00000601380.4	c.179C>A	p.Ala60Asp	missense_variant	1/14	5	NM_001276713.2	P1

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2163 AN: 152132 Hom.: 45 Cov.: 31

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.00168 AC: 1811 AN: 1079652 Hom.: 31 Cov.: 31 AF XY: 0.00167 AC XY: 850 AN XY: 509698

Gnomad4 AFR exome AF: 0.0494

Gnomad4 AMR exome AF: 0.00499

Gnomad4 ASJ exome AF: 0.000208

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000103

Gnomad4 FIN exome AF: 0.000142

Gnomad4 NFE exome AF: 0.000421

Gnomad4 OTH exome AF: 0.00467

GnomAD4 genome AF: 0.0142 AC: 2160 AN: 152250 Hom.: 45 Cov.: 31 AF XY: 0.0139 AC XY: 1033 AN XY: 74424

Gnomad4 AFR AF: 0.0479

Gnomad4 AMR AF: 0.00614

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.000347 Hom.: 0

Bravo AF: 0.0173

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00347 AC: 23

Asia WGS AF: 0.00318 AC: 11 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	16
Dann	Benign	0.92
DEOGEN2	Benign	0.00068	T
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0038	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.47	T
Sift4G	Benign	0.52	T
Vest4		0.27
MVP		0.42
GERP RS		1.6
Varity_R		0.092
gMVP		0.21

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: rs79228722; hg19: chr5-74907638;