19-4183685-A-G

Variant names:

• chr19-4183685-A-G
• rs4359565
• NM_001393985.1:c.-37+945A>G

Variant summary

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

The NM_001393985.1(ANKRD24):​c.-37+945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 152,072 control chromosomes in the GnomAD database, including 732 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 0.065 (732 hom., cov: 31)
• Consequence: ANKRD24 NM_001393985.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 3 publications found

Genes affected

ANKRD24 (HGNC:29424): (ankyrin repeat domain 24)

ANKRD24 Gene-Disease associations (from GenCC):

• sensorineural hearing loss disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD24	NM_001393985.1	c.-37+945A>G		intron_variant	Intron 1 of 21	ENST00000318934.9	NP_001380914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD24	ENST00000318934.9	c.-37+945A>G		intron_variant	Intron 1 of 21	5	NM_001393985.1	ENSP00000321731.4
ANKRD24	ENST00000600132.5	c.-153+208A>G		intron_variant	Intron 1 of 21	5		ENSP00000471252.1

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9782 AN: 151954 Hom.: 729 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.0482

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00907

Gnomad OTH AF: 0.0580

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0646 AC: 9821 AN: 152072 Hom.: 732 Cov.: 31 AF XY: 0.0675 AC XY: 5018 AN XY: 74348

African (AFR) AF: 0.161 AC: 6689 AN: 41462

American (AMR) AF: 0.0402 AC: 614 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0482 AC: 167 AN: 3468

East Asian (EAS) AF: 0.187 AC: 955 AN: 5110

South Asian (SAS) AF: 0.129 AC: 619 AN: 4816

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10620

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00909 AC: 618 AN: 68000

Other (OTH) AF: 0.0602 AC: 127 AN: 2110

Alfa AF: 0.0421 Hom.: 58

Bravo AF: 0.0713

Asia WGS AF: 0.164 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.097
PhyloP100		-2.9
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4359565; hg19: chr19-4183682;