10-90915892-GAA-GA

Variant names:

• chr10-90915892-GA-G
• rs3839929
• NM_014391.3:c.652-13delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_014391.3(ANKRD1):​c.652-13delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,611,048 control chromosomes in the GnomAD database, including 20,419 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2332 hom., cov: 25)
  • Exomes 𝑓: 0.16 (18087 hom.)
• Consequence: ANKRD1 NM_014391.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.87
• Publications: 6 publications found

Genes affected

ANKRD1 (HGNC:15819): (ankyrin repeat domain 1) The protein encoded by this gene is localized to the nucleus of endothelial cells and is induced by IL-1 and TNF-alpha stimulation. Studies in rat cardiomyocytes suggest that this gene functions as a transcription factor. Interactions between this protein and the sarcomeric proteins myopalladin and titin suggest that it may also be involved in the myofibrillar stretch-sensor system. [provided by RefSeq, Jul 2008]

ANKRD1 Gene-Disease associations (from GenCC):

• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 10-90915892-GA-G is Benign according to our data. Variant chr10-90915892-GA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 201661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014391.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	NM_014391.3	MANE Select	c.652-13delT		intron	N/A	NP_055206.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	ENST00000371697.4	TSL:1 MANE Select	c.652-13delT		intron	N/A	ENSP00000360762.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26111 AN: 151198 Hom.: 2326 Cov.: 25

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.0474

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.150 AC: 37486 AN: 249262 AF XY: 0.151

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.153

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.155 AC: 226340 AN: 1459732 Hom.: 18087 Cov.: 30 AF XY: 0.155 AC XY: 112313 AN XY: 726162

African (AFR) AF: 0.230 AC: 7693 AN: 33408

American (AMR) AF: 0.115 AC: 5155 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2738 AN: 26128

East Asian (EAS) AF: 0.160 AC: 6336 AN: 39622

South Asian (SAS) AF: 0.139 AC: 11987 AN: 86108

European-Finnish (FIN) AF: 0.151 AC: 8079 AN: 53348

Middle Eastern (MID) AF: 0.101 AC: 488 AN: 4836

European-Non Finnish (NFE) AF: 0.157 AC: 174801 AN: 1111332

Other (OTH) AF: 0.150 AC: 9063 AN: 60260

GnomAD4 genome AF: 0.173 AC: 26145 AN: 151316 Hom.: 2332 Cov.: 25 AF XY: 0.171 AC XY: 12627 AN XY: 73900

African (AFR) AF: 0.225 AC: 9236 AN: 41140

American (AMR) AF: 0.140 AC: 2126 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3462

East Asian (EAS) AF: 0.156 AC: 799 AN: 5118

South Asian (SAS) AF: 0.138 AC: 653 AN: 4746

European-Finnish (FIN) AF: 0.150 AC: 1566 AN: 10472

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.162 AC: 11011 AN: 67860

Other (OTH) AF: 0.134 AC: 281 AN: 2098

Alfa AF: 0.166 Hom.: 383

Bravo AF: 0.172

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ANKRD1-related dilated cardiomyopathy (1)
-	-	1	Dilated Cardiomyopathy, Dominant (1)
-	-	1	Hypertrophic cardiomyopathy 2 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3839929; hg19: chr10-92675649; COSMIC: COSV107477281;