rs3729828

Variant names:

• chr14-23416788-G-A
• rs3729828
• NM_000257.4:c.4644+80C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-23416788-G-A
• chr14-23416788-G-T

Variant summary

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

The NM_000257.4(MYH7):​c.4644+80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,606,016 control chromosomes in the GnomAD database, including 110,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (15633 hom., cov: 32)
  • Exomes 𝑓: 0.35 (94436 hom.)
• Consequence: MYH7 NM_000257.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0780
• Publications: 5 publications found

Genes affected

MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

MHRT (HGNC:51291): (myosin heavy chain associated RNA transcript) This gene encodes a spliced long non-coding RNA that may act as a cardioprotective agent in the heart. Based on a study of a similar gene in mouse, the encoded transcript may regulate chromatin remodeling by acting as a decoy to the BRG1 chromatin repressor complex thus preventing it from binding to its genomic targets. Blocking the actions of BRG1 could be crucial in protecting the heart from pathological hypertrophy. [provided by RefSeq, Dec 2014]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 14-23416788-G-A is Benign according to our data. Variant chr14-23416788-G-A is described in ClinVar as Benign. ClinVar VariationId is 1225999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000257.4. 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
	MYH7	NM_000257.4	MANE Select	c.4644+80C>T		intron	N/A	NP_000248.2	P12883
	MYH7	NM_001407004.1		c.4644+80C>T		intron	N/A	NP_001393933.1	P12883
	MHRT	NR_126491.1		n.559-128G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7	ENST00000355349.4	TSL:1 MANE Select	c.4644+80C>T		intron	N/A	ENSP00000347507.3	P12883
	MYH7	ENST00000858540.1		c.4644+80C>T		intron	N/A	ENSP00000528599.1
	MYH7	ENST00000965955.1		c.4644+80C>T		intron	N/A	ENSP00000636014.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63899 AN: 151932 Hom.: 15600 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.0771

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.349 AC: 507051 AN: 1453966 Hom.: 94436 AF XY: 0.345 AC XY: 249290 AN XY: 723422

African (AFR) AF: 0.686 AC: 22895 AN: 33376

American (AMR) AF: 0.198 AC: 8824 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 10394 AN: 26090

East Asian (EAS) AF: 0.0525 AC: 2080 AN: 39626

South Asian (SAS) AF: 0.225 AC: 19309 AN: 85870

European-Finnish (FIN) AF: 0.272 AC: 13494 AN: 49648

Middle Eastern (MID) AF: 0.327 AC: 1530 AN: 4672

European-Non Finnish (NFE) AF: 0.367 AC: 407508 AN: 1109988

Other (OTH) AF: 0.350 AC: 21017 AN: 60062

GnomAD4 genome AF: 0.421 AC: 63969 AN: 152050 Hom.: 15633 Cov.: 32 AF XY: 0.408 AC XY: 30308 AN XY: 74332

African (AFR) AF: 0.676 AC: 28043 AN: 41484

American (AMR) AF: 0.288 AC: 4398 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3466

East Asian (EAS) AF: 0.0773 AC: 399 AN: 5164

South Asian (SAS) AF: 0.215 AC: 1037 AN: 4816

European-Finnish (FIN) AF: 0.262 AC: 2772 AN: 10576

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24653 AN: 67942

Other (OTH) AF: 0.411 AC: 869 AN: 2112

Alfa AF: 0.506 Hom.: 4864

Bravo AF: 0.432

Asia WGS AF: 0.187 AC: 652 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		-0.078
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: rs3729828; hg19: chr14-23885997;