chr22-25877883-G-C

Variant names:

• chr22-25877883-G-C
• rs695428
• NM_032608.7:c.4225-76G>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.4225-76G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 1,244,174 control chromosomes in the GnomAD database, including 396,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50230 hom., cov: 33)
  • Exomes 𝑓: 0.79 (345933 hom.)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.138
• 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: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 22-25877883-G-C is Benign according to our data. Variant chr22-25877883-G-C is described in ClinVar as Benign. ClinVar VariationId is 1288011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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.4225-76G>C		intron	N/A	NP_115997.5
	MYO18B	NM_001318245.2		c.4228-76G>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.4225-76G>C		intron	N/A	ENSP00000334563.8	Q8IUG5-1
	MYO18B	ENST00000407587.6	TSL:1	c.4228-76G>C		intron	N/A	ENSP00000386096.2	Q8IUG5-3
	MYO18B	ENST00000536101.5	TSL:1	c.4225-76G>C		intron	N/A	ENSP00000441229.1	Q8IUG5-1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123143 AN: 152118 Hom.: 50175 Cov.: 33

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.794 AC: 867210 AN: 1091938 Hom.: 345933 AF XY: 0.795 AC XY: 436288 AN XY: 548580

African (AFR) AF: 0.853 AC: 21451 AN: 25152

American (AMR) AF: 0.864 AC: 26810 AN: 31034

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 14213 AN: 21656

East Asian (EAS) AF: 1.00 AC: 33708 AN: 33722

South Asian (SAS) AF: 0.862 AC: 58673 AN: 68074

European-Finnish (FIN) AF: 0.823 AC: 39533 AN: 48008

Middle Eastern (MID) AF: 0.767 AC: 3805 AN: 4962

European-Non Finnish (NFE) AF: 0.778 AC: 631552 AN: 811892

Other (OTH) AF: 0.790 AC: 37465 AN: 47438

GnomAD4 genome AF: 0.810 AC: 123259 AN: 152236 Hom.: 50230 Cov.: 33 AF XY: 0.815 AC XY: 60619 AN XY: 74422

African (AFR) AF: 0.849 AC: 35245 AN: 41526

American (AMR) AF: 0.814 AC: 12448 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2295 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5178 AN: 5192

South Asian (SAS) AF: 0.876 AC: 4226 AN: 4824

European-Finnish (FIN) AF: 0.834 AC: 8828 AN: 10590

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52498 AN: 68016

Other (OTH) AF: 0.773 AC: 1630 AN: 2110

Alfa AF: 0.721 Hom.: 2122

Bravo AF: 0.810

Asia WGS AF: 0.931 AC: 3237 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	-0.96
CADD	Benign	5.4
DANN	Benign	0.29
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs695428; hg19: chr22-26273850;