rs79793575

Variant names:

• chr10-90919284-G-A
• rs79793575
• NM_014391.3:c.208-16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014391.3(ANKRD1):​c.208-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,593,276 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (64 hom.)
• Consequence: ANKRD1 NM_014391.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.296
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-90919284-G-A is Benign according to our data. Variant chr10-90919284-G-A is described in ClinVar as Benign. ClinVar VariationId is 136401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0517 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.208-16C>T		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.208-16C>T		intron	N/A	ENSP00000360762.3	Q15327
	ANKRD1	ENST00000869698.1		c.208-16C>T		intron	N/A	ENSP00000539757.1
	ANKRD1	ENST00000945870.1		c.208-16C>T		intron	N/A	ENSP00000615929.1

Frequencies

GnomAD3 genomes AF: 0.00224 AC: 340 AN: 151974 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00530 AC: 1253 AN: 236620 AF XY: 0.00489

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000594

Gnomad ASJ exome AF: 0.00364

Gnomad EAS exome AF: 0.0656

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000166

Gnomad OTH exome AF: 0.00170

GnomAD4 exome AF: 0.00158 AC: 2277 AN: 1441184 Hom.: 64 Cov.: 31 AF XY: 0.00164 AC XY: 1178 AN XY: 717298

African (AFR) AF: 0.00 AC: 0 AN: 32858

American (AMR) AF: 0.000182 AC: 8 AN: 43928

Ashkenazi Jewish (ASJ) AF: 0.00290 AC: 75 AN: 25874

East Asian (EAS) AF: 0.0471 AC: 1849 AN: 39224

South Asian (SAS) AF: 0.00168 AC: 143 AN: 84948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46028

Middle Eastern (MID) AF: 0.000415 AC: 2 AN: 4820

European-Non Finnish (NFE) AF: 0.0000625 AC: 69 AN: 1103900

Other (OTH) AF: 0.00220 AC: 131 AN: 59604

GnomAD4 genome AF: 0.00223 AC: 339 AN: 152092 Hom.: 10 Cov.: 32 AF XY: 0.00266 AC XY: 198 AN XY: 74346

African (AFR) AF: 0.0000723 AC: 3 AN: 41482

American (AMR) AF: 0.000262 AC: 4 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.0571 AC: 295 AN: 5168

South Asian (SAS) AF: 0.00291 AC: 14 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67986

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.000710 Hom.: 0

Bravo AF: 0.00286

Asia WGS AF: 0.0160 AC: 55 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Congenital total pulmonary venous return anomaly (2)
-	-	1	ANKRD1-related dilated cardiomyopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.23
DANN	Benign	0.79
PhyloP100		-0.30
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: rs79793575; hg19: chr10-92679041; COSMIC: COSV63311228; COSMIC: COSV63311228;