rs2243675

Variant names:

• chr8-6406295-G-A
• rs2243675
• ENST00000500118.5:n.286C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-6406295-G-A
• chr8-6406295-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000500118.5(MCPH1-DT):​n.286C>T 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 0.00000468 in 426,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: MCPH1-DT ENST00000500118.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 2 publications found

Genes affected

MCPH1-DT (HGNC:55599): (MCPH1 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCPH1-DT	NR_040040.1	n.254C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCPH1-DT	ENST00000500118.5	n.286C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
MCPH1-DT	ENST00000523225.2	n.319C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
MCPH1-DT	ENST00000606853.3	n.304C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151738 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000363 AC: 1 AN: 275236 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 140906

African (AFR) AF: 0.00 AC: 0 AN: 7158

American (AMR) AF: 0.00 AC: 0 AN: 8292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9680

East Asian (EAS) AF: 0.00 AC: 0 AN: 23000

South Asian (SAS) AF: 0.00 AC: 0 AN: 8790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1386

European-Non Finnish (NFE) AF: 0.00000567 AC: 1 AN: 176368

Other (OTH) AF: 0.00 AC: 0 AN: 17880

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151738 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74090

African (AFR) AF: 0.0000242 AC: 1 AN: 41354

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67844

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 2430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.2
DANN	Benign	0.96
PhyloP100		0.047
PromoterAI		0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2243675; hg19: chr8-6263816;