22-16576248-G-T

Variant names:

• chr22-16576248-G-T
• rs5746647
• ENST00000493696.2:n.2504C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000493696.2(KCNMB3P1):​n.2504C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,036 control chromosomes in the GnomAD database, including 61,702 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 0.90 (61702 hom., cov: 30)
  • Exomes 𝑓: 0.94 (25796 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNMB3P1 ENST00000493696.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 7 publications found

Genes affected

KCNMB3P1 (HGNC:6288): (KCNMB3 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMB3P1	ENST00000493696.2	n.2504C>A		non_coding_transcript_exon_variant	Exon 3 of 3	6

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136246 AN: 151918 Hom.: 61664 Cov.: 30

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.936

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.917

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.941 AC: 54676 AN: 58114 Hom.: 25796 Cov.: 0 AF XY: 0.940 AC XY: 25276 AN XY: 26902

African (AFR) AF: 0.761 AC: 2027 AN: 2662

American (AMR) AF: 0.948 AC: 1591 AN: 1678

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3399 AN: 3674

East Asian (EAS) AF: 0.988 AC: 8760 AN: 8868

South Asian (SAS) AF: 0.936 AC: 481 AN: 514

European-Finnish (FIN) AF: 0.950 AC: 38 AN: 40

Middle Eastern (MID) AF: 0.933 AC: 349 AN: 374

European-Non Finnish (NFE) AF: 0.946 AC: 33586 AN: 35488

Other (OTH) AF: 0.923 AC: 4445 AN: 4816

GnomAD4 genome AF: 0.897 AC: 136342 AN: 152036 Hom.: 61702 Cov.: 30 AF XY: 0.898 AC XY: 66763 AN XY: 74338

African (AFR) AF: 0.764 AC: 31670 AN: 41426

American (AMR) AF: 0.937 AC: 14309 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3211 AN: 3470

East Asian (EAS) AF: 0.989 AC: 5118 AN: 5176

South Asian (SAS) AF: 0.937 AC: 4507 AN: 4810

European-Finnish (FIN) AF: 0.944 AC: 10003 AN: 10598

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.949 AC: 64480 AN: 67974

Other (OTH) AF: 0.918 AC: 1939 AN: 2112

Alfa AF: 0.932 Hom.: 168693

Bravo AF: 0.891

Asia WGS AF: 0.954 AC: 3314 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.71
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs5746647; hg19: chr22-17057138;