rs4822667

Variant names:

• chr22-25877869-G-A
• rs4822667
• NM_032608.7:c.4225-90G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-25877869-G-A
• chr22-25877869-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032608.7(MYO18B):​c.4225-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 975,484 control chromosomes in the GnomAD database, including 509 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 0.023 (48 hom., cov: 33)
  • Exomes 𝑓: 0.029 (461 hom.)
• Consequence: MYO18B NM_032608.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3468/151962) while in subpopulation NFE AF= 0.0356 (2421/67926). AF 95% confidence interval is 0.0345. There are 48 homozygotes in gnomad4. There are 1585 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.4225-90G>A		intron_variant	Intron 24 of 43	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.4225-90G>A		intron_variant	Intron 24 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.4228-90G>A		intron_variant	Intron 24 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.4225-90G>A		intron_variant	Intron 24 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.*1683-90G>A		intron_variant	Intron 22 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3469 AN: 151842 Hom.: 48 Cov.: 33

Gnomad AFR AF: 0.00641

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0339

GnomAD4 exome AF: 0.0291 AC: 23973 AN: 823522 Hom.: 461 AF XY: 0.0281 AC XY: 11849 AN XY: 421944

Gnomad4 AFR exome AF: 0.00644

Gnomad4 AMR exome AF: 0.0202

Gnomad4 ASJ exome AF: 0.0302

Gnomad4 EAS exome AF: 0.0000312

Gnomad4 SAS exome AF: 0.00169

Gnomad4 FIN exome AF: 0.0174

Gnomad4 NFE exome AF: 0.0360

Gnomad4 OTH exome AF: 0.0281

GnomAD4 genome AF: 0.0228 AC: 3468 AN: 151962 Hom.: 48 Cov.: 33 AF XY: 0.0213 AC XY: 1585 AN XY: 74268

Gnomad4 AFR AF: 0.00639

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0356

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.00447 Hom.: 1678

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.63
DANN	Benign	0.96

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: rs4822667; hg19: chr22-26273836;