rs4822668

Variant names:

• chr22-25877926-G-C
• rs4822668
• NM_032608.7:c.4225-33G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-25877926-G-C
• chr22-25877926-G-A
• chr22-25877926-G-T

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.4225-33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,537,184 control chromosomes in the GnomAD database, including 164,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.44 (14898 hom., cov: 32)
  • Exomes 𝑓: 0.46 (149795 hom.)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0300
• Publications: 5 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-25877926-G-C is Benign according to our data. Variant chr22-25877926-G-C is described in ClinVar as Benign. ClinVar VariationId is 1243210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.559 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.4225-33G>C		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.4228-33G>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.4225-33G>C		intron	N/A	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.4228-33G>C		intron	N/A	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.4225-33G>C		intron	N/A	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66136 AN: 151946 Hom.: 14889 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.418

GnomAD2 exomes AF: 0.478 AC: 77637 AN: 162462 AF XY: 0.468

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.386

Gnomad EAS exome AF: 0.431

Gnomad FIN exome AF: 0.493

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.459

GnomAD4 exome AF: 0.462 AC: 639519 AN: 1385120 Hom.: 149795 Cov.: 23 AF XY: 0.461 AC XY: 315710 AN XY: 684596

African (AFR) AF: 0.313 AC: 9817 AN: 31386

American (AMR) AF: 0.653 AC: 23368 AN: 35772

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 9691 AN: 25024

East Asian (EAS) AF: 0.473 AC: 16999 AN: 35916

South Asian (SAS) AF: 0.421 AC: 33122 AN: 78732

European-Finnish (FIN) AF: 0.491 AC: 24362 AN: 49584

Middle Eastern (MID) AF: 0.384 AC: 2177 AN: 5670

European-Non Finnish (NFE) AF: 0.465 AC: 494930 AN: 1065402

Other (OTH) AF: 0.435 AC: 25053 AN: 57634

GnomAD4 genome AF: 0.435 AC: 66163 AN: 152064 Hom.: 14898 Cov.: 32 AF XY: 0.438 AC XY: 32567 AN XY: 74316

African (AFR) AF: 0.329 AC: 13650 AN: 41492

American (AMR) AF: 0.569 AC: 8691 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1362 AN: 3468

East Asian (EAS) AF: 0.439 AC: 2271 AN: 5178

South Asian (SAS) AF: 0.416 AC: 2000 AN: 4804

European-Finnish (FIN) AF: 0.500 AC: 5282 AN: 10556

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31573 AN: 67988

Other (OTH) AF: 0.417 AC: 878 AN: 2108

Alfa AF: 0.445 Hom.: 2810

Bravo AF: 0.436

Asia WGS AF: 0.442 AC: 1536 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	-0.87
CADD	Benign	1.8
DANN	Benign	0.30
PhyloP100		-0.030
BranchPoint Hunter		0.0
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: rs4822668; hg19: chr22-26273893;