1-109296211-T-C

Variant names:

• chr1-109296211-T-C
• rs616899
• NM_001010985.3:c.867+23A>G

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.867+23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,611,356 control chromosomes in the GnomAD database, including 796,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71754 hom., cov: 30)
  • Exomes 𝑓: 1.0 (724920 hom.)
• Consequence: MYBPHL NM_001010985.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.388
• Publications: 6 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=-0.89).
• BP6: Variant 1-109296211-T-C is Benign according to our data. Variant chr1-109296211-T-C is described in ClinVar as Benign. ClinVar VariationId is 1282714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.867+23A>G		intron	N/A	NP_001010985.2	A2RUH7-1
	MYBPHL	NM_001265613.2		c.798+23A>G		intron	N/A	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.867+23A>G		intron	N/A	ENSP00000349678.1	A2RUH7-1
	MYBPHL	ENST00000477962.1	TSL:1	n.150-914A>G		intron	N/A
	MYBPHL	ENST00000968920.1		c.1047+23A>G		intron	N/A	ENSP00000638979.1

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147535 AN: 152102 Hom.: 71710 Cov.: 30

Gnomad AFR AF: 0.896

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.981

GnomAD2 exomes AF: 0.992 AC: 248068 AN: 250074 AF XY: 0.994

Gnomad AFR exome AF: 0.893

Gnomad AMR exome AF: 0.996

Gnomad ASJ exome AF: 0.996

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.997 AC: 1454263 AN: 1459136 Hom.: 724920 Cov.: 46 AF XY: 0.997 AC XY: 723753 AN XY: 725880

African (AFR) AF: 0.893 AC: 29789 AN: 33358

American (AMR) AF: 0.995 AC: 44114 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 25930 AN: 26058

East Asian (EAS) AF: 1.00 AC: 39676 AN: 39678

South Asian (SAS) AF: 1.00 AC: 86133 AN: 86150

European-Finnish (FIN) AF: 1.00 AC: 53325 AN: 53334

Middle Eastern (MID) AF: 0.991 AC: 4607 AN: 4648

European-Non Finnish (NFE) AF: 1.00 AC: 1110923 AN: 1111384

Other (OTH) AF: 0.993 AC: 59766 AN: 60190

GnomAD4 genome AF: 0.970 AC: 147635 AN: 152220 Hom.: 71754 Cov.: 30 AF XY: 0.971 AC XY: 72244 AN XY: 74416

African (AFR) AF: 0.896 AC: 37180 AN: 41488

American (AMR) AF: 0.988 AC: 15118 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3464 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5166

South Asian (SAS) AF: 0.999 AC: 4814 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 68000 AN: 68038

Other (OTH) AF: 0.981 AC: 2076 AN: 2116

Alfa AF: 0.992 Hom.: 8326

Bravo AF: 0.967

Asia WGS AF: 0.991 AC: 3446 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	-0.89
CADD	Benign	6.2
DANN	Benign	0.52
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs616899; hg19: chr1-109838833;