5-75611640-C-G

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.6C>G(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,231,354 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (39 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (35 hom.)
• Consequence: ANKDD1B NM_001276713.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.920

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=0.0034317076).
• BP6: Variant 5-75611640-C-G is Benign according to our data. Variant chr5-75611640-C-G is described in ClinVar as [Benign]. Clinvar id is 776047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1870/152032) while in subpopulation AFR AF= 0.0429 (1777/41426). AF 95% confidence interval is 0.0412. There are 39 homozygotes in gnomad4. There are 910 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKDD1B	NM_001276713.2	c.6C>G	p.Asp2Glu	missense_variant	1/14	ENST00000601380.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKDD1B	ENST00000601380.4	c.6C>G	p.Asp2Glu	missense_variant	1/14	5	NM_001276713.2	P1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1865 AN: 151914 Hom.: 40 Cov.: 31

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00121 AC: 1307 AN: 1079322 Hom.: 35 Cov.: 30 AF XY: 0.00113 AC XY: 576 AN XY: 509634

Gnomad4 AFR exome AF: 0.0461

Gnomad4 AMR exome AF: 0.00333

Gnomad4 ASJ exome AF: 0.00278

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000103

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000391

Gnomad4 OTH exome AF: 0.00309

GnomAD4 genome AF: 0.0123 AC: 1870 AN: 152032 Hom.: 39 Cov.: 31 AF XY: 0.0122 AC XY: 910 AN XY: 74338

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00197 Hom.: 1

Bravo AF: 0.0145

ExAC AF: 0.000289 AC: 1

Asia WGS AF: 0.00318 AC: 13 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
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.53
Dann	Benign	0.64
DEOGEN2	Benign	0.0045	T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0034	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.69	T
Sift4G	Pathogenic	0.0	D
Vest4		0.039
MVP		0.34
GERP RS		-0.055
Varity_R		0.036
gMVP		0.042

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: rs114367272; hg19: chr5-74907465;