rs7956194

chr12-109440020-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1H	NM_001101421.4	c.2454+230G>A		intron_variant		ENST00000310903.10
MYO1H	XM_011538223.3	c.2472+230G>A		intron_variant
MYO1H	XM_047428738.1	c.2406+230G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1H	ENST00000310903.10	c.2454+230G>A		intron_variant		5	NM_001101421.4	P1
MYO1H	ENST00000542268.5	n.254+230G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.426

Alfa AF: 0.398 Hom.: 2944

Bravo AF: 0.412

Asia WGS AF: 0.304 AC: 1031 AN: 3388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.8
Dann	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs7956194; hg19: chr12-109877825;