9-38575614-T-C

Position:

• chr9-38575614-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000399703.6(ANKRD18A):​c.2826A>G​(p.Thr942=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 1,551,522 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (36 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (40 hom.)
• Consequence: ANKRD18A ENST00000399703.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.59

Genes affected

ANKRD18A (HGNC:23643): (ankyrin repeat domain 18A)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 9-38575614-T-C is Benign according to our data. Variant chr9-38575614-T-C is described in ClinVar as [Benign]. Clinvar id is 780802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.59 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (2003/152346) while in subpopulation AFR AF= 0.041 (1705/41576). AF 95% confidence interval is 0.0394. There are 36 homozygotes in gnomad4. There are 897 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD18A	NM_147195.4	c.2826A>G	p.Thr942=	synonymous_variant	15/16	ENST00000399703.6	NP_671728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD18A	ENST00000399703.6	c.2826A>G	p.Thr942=	synonymous_variant	15/16	1	NM_147195.4	ENSP00000382610	A2

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1995 AN: 152228 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00449 AC: 706 AN: 157378 Hom.: 11 AF XY: 0.00375 AC XY: 312 AN XY: 83136

Gnomad AFR exome AF: 0.0398

Gnomad AMR exome AF: 0.00308

Gnomad ASJ exome AF: 0.000117

Gnomad EAS exome AF: 0.00863

Gnomad SAS exome AF: 0.00220

Gnomad FIN exome AF: 0.000118

Gnomad NFE exome AF: 0.00229

Gnomad OTH exome AF: 0.00429

GnomAD4 exome AF: 0.00354 AC: 4954 AN: 1399176 Hom.: 40 Cov.: 31 AF XY: 0.00352 AC XY: 2431 AN XY: 690084

Gnomad4 AFR exome AF: 0.0406

Gnomad4 AMR exome AF: 0.00333

Gnomad4 ASJ exome AF: 0.0000795

Gnomad4 EAS exome AF: 0.00336

Gnomad4 SAS exome AF: 0.00258

Gnomad4 FIN exome AF: 0.000101

Gnomad4 NFE exome AF: 0.00267

Gnomad4 OTH exome AF: 0.00525

GnomAD4 genome AF: 0.0131 AC: 2003 AN: 152346 Hom.: 36 Cov.: 32 AF XY: 0.0120 AC XY: 897 AN XY: 74500

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.00627

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00867

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00173

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00668 Hom.: 5

Bravo AF: 0.0144

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.016
DANN	Benign	0.24

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: rs12001355; hg19: chr9-38575611;