1-109294170-G-C

Position:

• chr1-109294170-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001010985.3(MYBPHL):​c.*33+36C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,351,274 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (124 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (120 hom.)
• Consequence: MYBPHL NM_001010985.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.373

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-109294170-G-C is Benign according to our data. Variant chr1-109294170-G-C is described in ClinVar as [Benign]. Clinvar id is 1268365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYBPHL	NM_001010985.3	c.*33+36C>G		intron_variant		ENST00000357155.2	NP_001010985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYBPHL	ENST00000357155.2	c.*33+36C>G		intron_variant		1	NM_001010985.3	ENSP00000349678	P1
MYBPHL	ENST00000477962.1	n.380+36C>G		intron_variant, non_coding_transcript_variant		1
MYBPHL	ENST00000489706.5	n.351+36C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3354 AN: 152166 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.00294 AC: 3523 AN: 1198990 Hom.: 120 Cov.: 17 AF XY: 0.00253 AC XY: 1546 AN XY: 610112

Gnomad4 AFR exome AF: 0.0853

Gnomad4 AMR exome AF: 0.00404

Gnomad4 ASJ exome AF: 0.00511

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000136

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000403

Gnomad4 OTH exome AF: 0.00624

GnomAD4 genome AF: 0.0222 AC: 3379 AN: 152284 Hom.: 124 Cov.: 32 AF XY: 0.0213 AC XY: 1586 AN XY: 74462

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.00889

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0157 Hom.: 6

Bravo AF: 0.0252

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.68
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17036114; hg19: chr1-109836792;