NM_032608.7:c.4225-137T>C

Variant names:

• chr22-25877822-T-C
• rs5761293
• NM_032608.7:c.4225-137T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032608.7(MYO18B):​c.4225-137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 629,792 control chromosomes in the GnomAD database, including 36,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9582 hom., cov: 32)
  • Exomes 𝑓: 0.33 (26510 hom.)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.60
• Publications: 0 publications found

Genes affected

MYO18B (HGNC:18150): (myosin XVIIIB) The protein encoded by this gene may regulate muscle-specific genes when in the nucleus and may influence intracellular trafficking when in the cytoplasm. The encoded protein functions as a homodimer and may interact with F actin. Mutations in this gene are associated with lung cancer. [provided by RefSeq, Jul 2008]

MYO18B-AS1 (HGNC:40831): (MYO18B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 22-25877822-T-C is Benign according to our data. Variant chr22-25877822-T-C is described in ClinVar as Benign. ClinVar VariationId is 1239538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032608.7. 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
	MYO18B	NM_032608.7	MANE Select	c.4225-137T>C		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.4228-137T>C		intron	N/A	NP_001305174.1	Q8IUG5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO18B	ENST00000335473.12	TSL:1 MANE Select	c.4225-137T>C		intron	N/A	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.4228-137T>C		intron	N/A	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.4225-137T>C		intron	N/A	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52459 AN: 151964 Hom.: 9564 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.335

GnomAD4 exome AF: 0.326 AC: 155909 AN: 477708 Hom.: 26510 AF XY: 0.327 AC XY: 81813 AN XY: 250356

African (AFR) AF: 0.446 AC: 5248 AN: 11772

American (AMR) AF: 0.215 AC: 3479 AN: 16146

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 3453 AN: 13264

East Asian (EAS) AF: 0.475 AC: 13118 AN: 27622

South Asian (SAS) AF: 0.359 AC: 15214 AN: 42354

European-Finnish (FIN) AF: 0.335 AC: 13683 AN: 40806

Middle Eastern (MID) AF: 0.391 AC: 1353 AN: 3462

European-Non Finnish (NFE) AF: 0.309 AC: 91668 AN: 296478

Other (OTH) AF: 0.337 AC: 8693 AN: 25804

GnomAD4 genome AF: 0.345 AC: 52517 AN: 152084 Hom.: 9582 Cov.: 32 AF XY: 0.346 AC XY: 25706 AN XY: 74342

African (AFR) AF: 0.437 AC: 18120 AN: 41452

American (AMR) AF: 0.236 AC: 3605 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 905 AN: 3462

East Asian (EAS) AF: 0.497 AC: 2571 AN: 5170

South Asian (SAS) AF: 0.360 AC: 1733 AN: 4820

European-Finnish (FIN) AF: 0.334 AC: 3529 AN: 10574

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20887 AN: 68000

Other (OTH) AF: 0.339 AC: 717 AN: 2112

Alfa AF: 0.319 Hom.: 1622

Bravo AF: 0.343

Asia WGS AF: 0.423 AC: 1469 AN: 3478

ClinVar

ClinVar submissions

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	-1.0
CADD	Benign	0.74
DANN	Benign	0.31
PhyloP100		-1.6
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: rs5761293; hg19: chr22-26273789; COSMIC: COSV59133582;