rs4791407

Variant names:

• chr17-10414525-A-G
• rs4791407
• NM_002472.3:c.806-41T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-10414525-A-G
• chr17-10414525-A-C
• chr17-10414525-A-T

Variant summary

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

The NM_002472.3(MYH8):​c.806-41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,335,672 control chromosomes in the GnomAD database, including 142,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14488 hom., cov: 32)
  • Exomes 𝑓: 0.45 (127586 hom.)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.02
• Publications: 7 publications found

Genes affected

MYH8 (HGNC:7578): (myosin heavy chain 8) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-10414525-A-G is Benign according to our data. Variant chr17-10414525-A-G is described in ClinVar as Benign. ClinVar VariationId is 1179638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002472.3. 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
	MYH8	NM_002472.3	MANE Select	c.806-41T>C		intron	N/A	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.167+8287A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	ENST00000403437.2	TSL:5 MANE Select	c.806-41T>C		intron	N/A	ENSP00000384330.2	P13535
	MYHAS	ENST00000399342.6	TSL:3	n.206+8248A>G		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.143+8287A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63932 AN: 151860 Hom.: 14479 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.395

GnomAD2 exomes AF: 0.516 AC: 114299 AN: 221648 AF XY: 0.516

Gnomad AFR exome AF: 0.309

Gnomad AMR exome AF: 0.608

Gnomad ASJ exome AF: 0.462

Gnomad EAS exome AF: 0.888

Gnomad FIN exome AF: 0.480

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.464

GnomAD4 exome AF: 0.451 AC: 533464 AN: 1183696 Hom.: 127586 Cov.: 16 AF XY: 0.456 AC XY: 274175 AN XY: 600842

African (AFR) AF: 0.300 AC: 8368 AN: 27872

American (AMR) AF: 0.589 AC: 25403 AN: 43138

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 11179 AN: 24142

East Asian (EAS) AF: 0.849 AC: 32329 AN: 38080

South Asian (SAS) AF: 0.648 AC: 51507 AN: 79512

European-Finnish (FIN) AF: 0.467 AC: 24093 AN: 51616

Middle Eastern (MID) AF: 0.435 AC: 2199 AN: 5052

European-Non Finnish (NFE) AF: 0.411 AC: 355012 AN: 863248

Other (OTH) AF: 0.458 AC: 23374 AN: 51036

GnomAD4 genome AF: 0.421 AC: 63979 AN: 151976 Hom.: 14488 Cov.: 32 AF XY: 0.434 AC XY: 32251 AN XY: 74264

African (AFR) AF: 0.306 AC: 12678 AN: 41484

American (AMR) AF: 0.493 AC: 7520 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3466

East Asian (EAS) AF: 0.867 AC: 4470 AN: 5156

South Asian (SAS) AF: 0.662 AC: 3183 AN: 4806

European-Finnish (FIN) AF: 0.480 AC: 5067 AN: 10552

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28067 AN: 67940

Other (OTH) AF: 0.396 AC: 837 AN: 2112

Alfa AF: 0.419 Hom.: 7672

Bravo AF: 0.413

Asia WGS AF: 0.724 AC: 2514 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	-0.87
CADD	Benign	0.038
DANN	Benign	0.42
PhyloP100		-1.0
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: rs4791407; hg19: chr17-10317842; COSMIC: COSV67961943;