1-109294220-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.480

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1222087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBPHL	NM_001010985.3	c.*19G>C		3_prime_UTR_variant	8/9	ENST00000357155.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBPHL	ENST00000357155.2	c.*19G>C		3_prime_UTR_variant	8/9	1	NM_001010985.3	P1
MYBPHL	ENST00000477962.1	n.366G>C		non_coding_transcript_exon_variant	3/4	1
MYBPHL	ENST00000489706.5	n.337G>C		non_coding_transcript_exon_variant	3/4	2

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

GnomAD3 exomes AF: 0.588 AC: 147702 AN: 251136 Hom.: 44022 AF XY: 0.587 AC XY: 79673 AN XY: 135750

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 SAS exome AF: 0.507

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

Gnomad4 AFR exome AF: 0.457

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.546

Gnomad4 EAS exome AF: 0.528

Gnomad4 SAS exome AF: 0.512

Gnomad4 FIN exome AF: 0.615

Gnomad4 NFE exome AF: 0.623

Gnomad4 OTH exome AF: 0.593

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

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.576

Alfa AF: 0.534 Hom.: 2966

Bravo AF: 0.566

Asia WGS AF: 0.527 AC: 1829 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	10
Dann	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs646335; hg19: chr1-109836842; COSMIC: COSV64062749;