NM_014391.3:c.346-19_346-14delTTATTT

Variant names:

• chr10-90918985-TAAATAA-T
• rs58762441
• NM_014391.3:c.346-19_346-14delTTATTT

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.346-19_346-14delTTATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 301,188 control chromosomes in the GnomAD database, including 4,516 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (2543 hom., cov: 0)
  • Exomes 𝑓: 0.14 (1973 hom.)
• Consequence: ANKRD1 NM_014391.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.19
• Publications: 2 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 -16 ACMG points.

• BP6: Variant 10-90918985-TAAATAA-T is Benign according to our data. Variant chr10-90918985-TAAATAA-T is described in ClinVar as Benign. ClinVar VariationId is 45632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	NM_014391.3	MANE Select	c.346-19_346-14delTTATTT		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.346-19_346-14delTTATTT		intron	N/A	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.346-19_346-14delTTATTT		intron	N/A	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.346-19_346-14delTTATTT		intron	N/A	ENSP00000615929.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 17302 AN: 63404 Hom.: 2543 Cov.: 0

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.251

GnomAD2 exomes AF: 0.0514 AC: 10913 AN: 212278 AF XY: 0.0495

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.0434

Gnomad ASJ exome AF: 0.0311

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.0458

Gnomad NFE exome AF: 0.0297

Gnomad OTH exome AF: 0.0367

GnomAD4 exome AF: 0.143 AC: 34049 AN: 237782 Hom.: 1973 AF XY: 0.144 AC XY: 17244 AN XY: 119524

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

African (AFR) AF: 0.403 AC: 3315 AN: 8222

American (AMR) AF: 0.350 AC: 1805 AN: 5150

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 657 AN: 4610

East Asian (EAS) AF: 0.339 AC: 3226 AN: 9528

South Asian (SAS) AF: 0.281 AC: 4162 AN: 14828

European-Finnish (FIN) AF: 0.177 AC: 1475 AN: 8324

Middle Eastern (MID) AF: 0.159 AC: 158 AN: 996

European-Non Finnish (NFE) AF: 0.0993 AC: 17435 AN: 175552

Other (OTH) AF: 0.172 AC: 1816 AN: 10572

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.273 AC: 17302 AN: 63406 Hom.: 2543 Cov.: 0 AF XY: 0.280 AC XY: 8573 AN XY: 30570

African (AFR) AF: 0.405 AC: 9598 AN: 23678

American (AMR) AF: 0.301 AC: 2020 AN: 6722

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 272 AN: 1346

East Asian (EAS) AF: 0.393 AC: 1050 AN: 2672

South Asian (SAS) AF: 0.320 AC: 680 AN: 2124

European-Finnish (FIN) AF: 0.227 AC: 617 AN: 2720

Middle Eastern (MID) AF: 0.279 AC: 34 AN: 122

European-Non Finnish (NFE) AF: 0.122 AC: 2779 AN: 22798

Other (OTH) AF: 0.251 AC: 242 AN: 964

Alfa AF: 0.106 Hom.: 85

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	ANKRD1-related dilated cardiomyopathy (1)
-	-	1	Congenital total pulmonary venous return anomaly (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs58762441; hg19: chr10-92678742;