rs57660219

Variant names:

• chr14-23389064-G-A
• rs57660219
• NM_002471.4:c.3979-9C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-23389064-G-A
• chr14-23389064-G-C
• chr14-23389064-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002471.4(MYH6):​c.3979-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000387 in 1,213,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000074 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: MYH6 NM_002471.4 intron
• Scores: Splicing: ADA: 0.00005156
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.427
• Publications: 1 publications found

Genes affected

MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]

MYH6 Gene-Disease associations (from GenCC):

• MYH-6 related congenital heart defects

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 14

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• Keppen-Lubinsky syndrome

  Inheritance: AD Classification: MODERATE Submitted by: Illumina
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• atrial septal defect 3

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 14-23389064-G-A is Benign according to our data. Variant chr14-23389064-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 774370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002471.4. 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
	MYH6	NM_002471.4	MANE Select	c.3979-9C>T		intron	N/A	NP_002462.2	P13533

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH6	ENST00000405093.9	TSL:5 MANE Select	c.3979-9C>T		intron	N/A	ENSP00000386041.3	P13533
	MYH6	ENST00000968262.1		c.4012-9C>T		intron	N/A	ENSP00000638321.1
	MYH6	ENST00000968257.1		c.3979-9C>T		intron	N/A	ENSP00000638316.1

Frequencies

GnomAD3 genomes AF: 0.0000738 AC: 5 AN: 67768 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000718

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000275

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000125 AC: 12 AN: 96074 AF XY: 0.000135

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000487

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000138

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.0000217

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000366 AC: 42 AN: 1146174 Hom.: 0 Cov.: 32 AF XY: 0.0000386 AC XY: 22 AN XY: 569900

African (AFR) AF: 0.000334 AC: 8 AN: 23918

American (AMR) AF: 0.000183 AC: 7 AN: 38212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17944

East Asian (EAS) AF: 0.0000260 AC: 1 AN: 38530

South Asian (SAS) AF: 0.000111 AC: 8 AN: 72082

European-Finnish (FIN) AF: 0.0000256 AC: 1 AN: 39016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4648

European-Non Finnish (NFE) AF: 0.00000810 AC: 7 AN: 864704

Other (OTH) AF: 0.000212 AC: 10 AN: 47120

GnomAD4 genome AF: 0.0000738 AC: 5 AN: 67768 Hom.: 0 Cov.: 0 AF XY: 0.000119 AC XY: 4 AN XY: 33648

African (AFR) AF: 0.00 AC: 0 AN: 6200

American (AMR) AF: 0.000113 AC: 1 AN: 8830

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1592

East Asian (EAS) AF: 0.000718 AC: 3 AN: 4178

South Asian (SAS) AF: 0.00 AC: 0 AN: 2608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 154

European-Non Finnish (NFE) AF: 0.0000275 AC: 1 AN: 36338

Other (OTH) AF: 0.00 AC: 0 AN: 910

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hypertrophic cardiomyopathy 14 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.4
DANN	Benign	0.96
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000052
dbscSNV1_RF	Benign	0.0
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: rs57660219; hg19: chr14-23858273;