chr2-170604622-T-C

Variant names:

• chr2-170604622-T-C
• rs6749331
• NM_138995.5:c.3734-47006T>C

Variant summary

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

The NM_138995.5(MYO3B):​c.3734-47006T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,044 control chromosomes in the GnomAD database, including 7,350 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 0.24 (7350 hom., cov: 32)
• Consequence: MYO3B NM_138995.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 7 publications found

Genes affected

MYO3B (HGNC:15576): (myosin IIIB) This gene encodes one of the class III myosins. Myosins are ATPases, activated by actin, that move along actin filaments in the cell. This class of myosins are characterized by an amino-terminal kinase domain and shown to be present in photoreceptors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO3B	NM_138995.5	c.3734-47006T>C		intron_variant	Intron 32 of 34	ENST00000408978.9	NP_620482.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO3B	ENST00000408978.9	c.3734-47006T>C		intron_variant	Intron 32 of 34	1	NM_138995.5	ENSP00000386213.4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35925 AN: 151926 Hom.: 7328 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0622

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.237 AC: 35993 AN: 152044 Hom.: 7350 Cov.: 32 AF XY: 0.231 AC XY: 17197 AN XY: 74324

African (AFR) AF: 0.557 AC: 23098 AN: 41444

American (AMR) AF: 0.148 AC: 2255 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3470

East Asian (EAS) AF: 0.0514 AC: 266 AN: 5178

South Asian (SAS) AF: 0.193 AC: 928 AN: 4820

European-Finnish (FIN) AF: 0.0622 AC: 658 AN: 10574

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7762 AN: 67958

Other (OTH) AF: 0.209 AC: 441 AN: 2108

Alfa AF: 0.185 Hom.: 7375

Bravo AF: 0.257

Asia WGS AF: 0.146 AC: 511 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.70
PhyloP100		-1.9
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: rs6749331; hg19: chr2-171461132;