rs16343

chr4-17633933-CAAAAT-Cchr4-17633933-CAAAAT-CAAAATAAAAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_025205.5(MED28):c.*10139_*10143del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,327,290 control chromosomes in the GnomAD database, including 238,215 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (23001 hom., cov: 0)
  • Exomes 𝑓: 0.60 (215214 hom.)
• Consequence: MED28 NM_025205.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

Genes affected

MED28 (HGNC:24628): (mediator complex subunit 28) Predicted to enable actin binding activity. Predicted to act upstream of or within negative regulation of smooth muscle cell differentiation and stem cell population maintenance. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM184B (HGNC:29235): (family with sequence similarity 184 member B)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED28	NM_025205.5	c.*10139_*10143del		3_prime_UTR_variant	4/4	ENST00000237380.12
FAM184B	NM_015688.2	c.2890-50_2890-46del		intron_variant		ENST00000265018.4
FAM184B	XM_047450066.1	c.2890-50_2890-46del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED28	ENST00000237380.12	c.*10139_*10143del		3_prime_UTR_variant	4/4	1	NM_025205.5	P1
FAM184B	ENST00000265018.4	c.2890-50_2890-46del		intron_variant		1	NM_015688.2	P1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77670 AN: 151504 Hom.: 22990 Cov.: 0

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.537

GnomAD3 exomes AF: 0.615 AC: 32944 AN: 53556 Hom.: 10667 AF XY: 0.610 AC XY: 16743 AN XY: 27458

Gnomad AFR exome AF: 0.194

Gnomad AMR exome AF: 0.723

Gnomad ASJ exome AF: 0.501

Gnomad EAS exome AF: 0.893

Gnomad SAS exome AF: 0.561

Gnomad FIN exome AF: 0.669

Gnomad NFE exome AF: 0.611

Gnomad OTH exome AF: 0.608

GnomAD4 exome AF: 0.598 AC: 702549 AN: 1175666 Hom.: 215214 AF XY: 0.598 AC XY: 340115 AN XY: 569026

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.688

Gnomad4 ASJ exome AF: 0.498

Gnomad4 EAS exome AF: 0.904

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.598

Gnomad4 OTH exome AF: 0.588

GnomAD4 genome AF: 0.512 AC: 77695 AN: 151624 Hom.: 23001 Cov.: 0 AF XY: 0.519 AC XY: 38451 AN XY: 74076

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.541

Alfa AF: 0.539 Hom.: 4160

Bravo AF: 0.500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16343; hg19: chr4-17635556;