NM_014391.3:c.346-18_346-9delTATTTATTTT

Variant names:

• chr10-90918980-CAAAATAAATA-C
• rs727502890
• NM_014391.3:c.346-18_346-9delTATTTATTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_014391.3(ANKRD1):​c.346-18_346-9delTATTTATTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 1,304,988 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: ANKRD1 NM_014391.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.19
• Publications: 1 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
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• 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 -8 ACMG points.

• BP6: Variant 10-90918980-CAAAATAAATA-C is Benign according to our data. Variant chr10-90918980-CAAAATAAATA-C is described in ClinVar as Likely_benign. ClinVar VariationId is 162748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	NM_014391.3	MANE Select	c.346-18_346-9delTATTTATTTT		intron	N/A	NP_055206.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	ENST00000371697.4	TSL:1 MANE Select	c.346-18_346-9delTATTTATTTT		intron	N/A	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.346-18_346-9delTATTTATTTT		intron	N/A	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.346-18_346-9delTATTTATTTT		intron	N/A	ENSP00000615929.1

Frequencies

GnomAD3 genomes AF: 0.0000227 AC: 1 AN: 44148 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00171

GnomAD2 exomes AF: 0.000155 AC: 30 AN: 193972 AF XY: 0.0000839

Gnomad AFR exome AF: 0.00147

Gnomad AMR exome AF: 0.0000359

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000146

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000100

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000270 AC: 34 AN: 1260840 Hom.: 0 AF XY: 0.0000237 AC XY: 15 AN XY: 633412

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000478 AC: 10 AN: 20920

American (AMR) AF: 0.00 AC: 0 AN: 41408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24424

East Asian (EAS) AF: 0.00 AC: 0 AN: 33340

South Asian (SAS) AF: 0.0000665 AC: 5 AN: 75174

European-Finnish (FIN) AF: 0.0000215 AC: 1 AN: 46562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5014

European-Non Finnish (NFE) AF: 0.0000187 AC: 18 AN: 961620

Other (OTH) AF: 0.00 AC: 0 AN: 52378

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000468591), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000227 AC: 1 AN: 44148 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20890

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6858

American (AMR) AF: 0.00 AC: 0 AN: 3558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1426

East Asian (EAS) AF: 0.00 AC: 0 AN: 1564

South Asian (SAS) AF: 0.00 AC: 0 AN: 1314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 124

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 25702

Other (OTH) AF: 0.00171 AC: 1 AN: 584

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000111 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	ANKRD1-related dilated cardiomyopathy (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs727502890; hg19: chr10-92678737;