12-109440020-G-A

Variant names:

• chr12-109440020-G-A
• rs7956194
• NM_001101421.4:c.2454+230G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001101421.4(MYO1H):​c.2454+230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,360 control chromosomes in the GnomAD database, including 12,155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12155 hom., cov: 31)
• Consequence: MYO1H NM_001101421.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 11 publications found

Genes affected

MYO1H (HGNC:13879): (myosin IH) Predicted to enable actin filament binding activity and microfilament motor activity. Predicted to be involved in actin filament organization and vesicle transport along actin filament. Predicted to be part of myosin complex. Predicted to be active in several cellular components, including actin cytoskeleton; microvillus; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

MYO1H Gene-Disease associations (from GenCC):

• congenital central hypoventilation syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• central hypoventilation syndrome, congenital, 2, and autonomic dysfunction

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101421.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1H	NM_001101421.4	MANE Select	c.2454+230G>A		intron	N/A	NP_001094891.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1H	ENST00000310903.10	TSL:5 MANE Select	c.2454+230G>A		intron	N/A	ENSP00000439182.2
	MYO1H	ENST00000542268.5	TSL:2	n.254+230G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60024 AN: 151260 Hom.: 12152 Cov.: 31

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.397 AC: 60059 AN: 151360 Hom.: 12155 Cov.: 31 AF XY: 0.391 AC XY: 28941 AN XY: 73936

African (AFR) AF: 0.434 AC: 17907 AN: 41262

American (AMR) AF: 0.407 AC: 6193 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3468

East Asian (EAS) AF: 0.393 AC: 2021 AN: 5144

South Asian (SAS) AF: 0.302 AC: 1446 AN: 4794

European-Finnish (FIN) AF: 0.316 AC: 3267 AN: 10350

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.383 AC: 25972 AN: 67802

Other (OTH) AF: 0.426 AC: 901 AN: 2116

Alfa AF: 0.403 Hom.: 4777

Bravo AF: 0.412

Asia WGS AF: 0.304 AC: 1031 AN: 3388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.30
PhyloP100		0.54
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: rs7956194; hg19: chr12-109877825;