rs2075440

Variant names:

• chr12-109421295-A-G
• rs2075440
• NM_001101421.4:c.1644+268A>G

Variant summary

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

The NM_001101421.4(MYO1H):​c.1644+268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,874 control chromosomes in the GnomAD database, including 20,456 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 0.51 (20456 hom., cov: 31)
• Consequence: MYO1H NM_001101421.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1H	NM_001101421.4	c.1644+268A>G		intron_variant	Intron 16 of 31	ENST00000310903.10	NP_001094891.4
MYO1H	XM_011538223.3	c.1596+268A>G		intron_variant	Intron 17 of 33		XP_011536525.1
MYO1H	XM_047428738.1	c.1596+268A>G		intron_variant	Intron 15 of 30		XP_047284694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1H	ENST00000310903.10	c.1644+268A>G		intron_variant	Intron 16 of 31	5	NM_001101421.4	ENSP00000439182.2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77095 AN: 151756 Hom.: 20422 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.508 AC: 77185 AN: 151874 Hom.: 20456 Cov.: 31 AF XY: 0.503 AC XY: 37292 AN XY: 74212

African (AFR) AF: 0.642 AC: 26566 AN: 41366

American (AMR) AF: 0.563 AC: 8588 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1902 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2303 AN: 5144

South Asian (SAS) AF: 0.340 AC: 1637 AN: 4810

European-Finnish (FIN) AF: 0.365 AC: 3850 AN: 10548

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30546 AN: 67954

Other (OTH) AF: 0.528 AC: 1115 AN: 2110

Alfa AF: 0.555 Hom.: 6362

Bravo AF: 0.536

Asia WGS AF: 0.380 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-0.23
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: rs2075440; hg19: chr12-109859100; COSMIC: COSV60451216;