rs11994063

Variant names:

• chr8-6643857-G-A
• rs11994063
• NM_024596.5:c.*808G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-6643857-G-A
• chr8-6643857-G-T

Variant summary

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

The NM_024596.5(MCPH1):​c.*808G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,146 control chromosomes in the GnomAD database, including 2,210 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 0.16 (2208 hom., cov: 32)
  • Exomes 𝑓: 0.27 (2 hom.)
• Consequence: MCPH1 NM_024596.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 7 publications found

Genes affected

MCPH1 (HGNC:6954): (microcephalin 1) This gene encodes a DNA damage response protein. The encoded protein may play a role in G2/M checkpoint arrest via maintenance of inhibitory phosphorylation of cyclin-dependent kinase 1. Mutations in this gene have been associated with primary autosomal recessive microcephaly 1 and premature chromosome condensation syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

MCPH1-AS1 (HGNC:51655): (MCPH1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCPH1	NM_024596.5	c.*808G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000344683.10	NP_078872.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCPH1	ENST00000344683.10	c.*808G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_024596.5	ENSP00000342924.5

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24368 AN: 151986 Hom.: 2210 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.273 AC: 12 AN: 44 Hom.: 2 Cov.: 0 AF XY: 0.346 AC XY: 9 AN XY: 26

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.278 AC: 10 AN: 36

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.160 AC: 24373 AN: 152102 Hom.: 2208 Cov.: 32 AF XY: 0.160 AC XY: 11936 AN XY: 74370

African (AFR) AF: 0.0923 AC: 3831 AN: 41498

American (AMR) AF: 0.117 AC: 1789 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3472

East Asian (EAS) AF: 0.0885 AC: 457 AN: 5166

South Asian (SAS) AF: 0.213 AC: 1023 AN: 4814

European-Finnish (FIN) AF: 0.195 AC: 2069 AN: 10596

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14077 AN: 67976

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.161 Hom.: 1417

Bravo AF: 0.150

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.69
PhyloP100		1.0

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

Other links and lift over

dbSNP: rs11994063; hg19: chr8-6501378;