1-109294220-C-G

Variant names:

• chr1-109294220-C-G
• rs646335
• NM_001010985.3:c.*19G>C

Variant summary

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

The NM_001010985.3(MYBPHL):​c.*19G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,595,752 control chromosomes in the GnomAD database, including 292,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25020 hom., cov: 32)
  • Exomes 𝑓: 0.61 (267575 hom.)
• Consequence: MYBPHL NM_001010985.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.480
• Publications: 13 publications found

Genes affected

MYBPHL (HGNC:30434): (myosin binding protein H like) This gene encodes a protein with two immunoglobulin superfamily domains and a fibronectin 3 domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

MYBPHL Gene-Disease associations (from GenCC):

• familial dilated cardiomyopathy

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-109294220-C-G is Benign according to our data. Variant chr1-109294220-C-G is described in ClinVar as Benign. ClinVar VariationId is 1222087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010985.3. 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
	MYBPHL	NM_001010985.3	MANE Select	c.*19G>C		3_prime_UTR	Exon 8 of 9	NP_001010985.2	A2RUH7-1
	MYBPHL	NM_001265613.2		c.*19G>C		3_prime_UTR	Exon 8 of 9	NP_001252542.1	A2RUH7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPHL	ENST00000357155.2	TSL:1 MANE Select	c.*19G>C		3_prime_UTR	Exon 8 of 9	ENSP00000349678.1	A2RUH7-1
	MYBPHL	ENST00000477962.1	TSL:1	n.366G>C		non_coding_transcript_exon	Exon 3 of 4
	MYBPHL	ENST00000968920.1		c.*19G>C		3_prime_UTR	Exon 8 of 9	ENSP00000638979.1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86312 AN: 151964 Hom.: 25002 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.573

GnomAD2 exomes AF: 0.588 AC: 147702 AN: 251136 AF XY: 0.587

Gnomad AFR exome AF: 0.472

Gnomad AMR exome AF: 0.621

Gnomad ASJ exome AF: 0.544

Gnomad EAS exome AF: 0.550

Gnomad FIN exome AF: 0.605

Gnomad NFE exome AF: 0.623

Gnomad OTH exome AF: 0.602

GnomAD4 exome AF: 0.607 AC: 875594 AN: 1443670 Hom.: 267575 Cov.: 28 AF XY: 0.604 AC XY: 434576 AN XY: 719314

African (AFR) AF: 0.457 AC: 15161 AN: 33176

American (AMR) AF: 0.609 AC: 27185 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 14197 AN: 25998

East Asian (EAS) AF: 0.528 AC: 20911 AN: 39590

South Asian (SAS) AF: 0.512 AC: 43915 AN: 85806

European-Finnish (FIN) AF: 0.615 AC: 32828 AN: 53360

Middle Eastern (MID) AF: 0.610 AC: 3500 AN: 5736

European-Non Finnish (NFE) AF: 0.623 AC: 682440 AN: 1095530

Other (OTH) AF: 0.593 AC: 35457 AN: 59822

GnomAD4 genome AF: 0.568 AC: 86369 AN: 152082 Hom.: 25020 Cov.: 32 AF XY: 0.565 AC XY: 41986 AN XY: 74342

African (AFR) AF: 0.467 AC: 19348 AN: 41456

American (AMR) AF: 0.600 AC: 9161 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1862 AN: 3466

East Asian (EAS) AF: 0.537 AC: 2779 AN: 5178

South Asian (SAS) AF: 0.491 AC: 2364 AN: 4816

European-Finnish (FIN) AF: 0.600 AC: 6354 AN: 10582

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.627 AC: 42629 AN: 67986

Other (OTH) AF: 0.576 AC: 1218 AN: 2116

Alfa AF: 0.534 Hom.: 2966

Bravo AF: 0.566

Asia WGS AF: 0.527 AC: 1829 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.82
CADD	Benign	10
DANN	Benign	0.53
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs646335; hg19: chr1-109836842; COSMIC: COSV64062749;