rs11774231

Variant names:

• chr8-6646795-C-T
• rs11774231
• NM_024596.5:c.*3746C>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.*3746C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 152,202 control chromosomes in the GnomAD database, including 381 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 0.063 (381 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: MCPH1 NM_024596.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.975
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024596.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCPH1	NM_024596.5	MANE Select	c.*3746C>T		3_prime_UTR	Exon 14 of 14	NP_078872.3	Q8NEM0-1
	MCPH1	NM_001322042.2		c.*3768C>T		3_prime_UTR	Exon 15 of 15	NP_001308971.2	A0A8I5KV10
	MCPH1	NM_001363980.2		c.*3746C>T		3_prime_UTR	Exon 11 of 11	NP_001350909.1	A0A8I5KR97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCPH1	ENST00000344683.10	TSL:1 MANE Select	c.*3746C>T		3_prime_UTR	Exon 14 of 14	ENSP00000342924.5	Q8NEM0-1
	MCPH1-AS1	ENST00000515608.5	TSL:5	n.525+1488G>A		intron	N/A
	MCPH1-AS1	ENST00000522897.1	TSL:4	n.61-19485G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9628 AN: 152084 Hom.: 382 Cov.: 33

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.0774

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0633 AC: 9632 AN: 152202 Hom.: 381 Cov.: 33 AF XY: 0.0616 AC XY: 4587 AN XY: 74422

African (AFR) AF: 0.0325 AC: 1349 AN: 41516

American (AMR) AF: 0.0537 AC: 821 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0982 AC: 473 AN: 4816

European-Finnish (FIN) AF: 0.0427 AC: 453 AN: 10602

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0861 AC: 5854 AN: 67994

Other (OTH) AF: 0.0766 AC: 162 AN: 2116

Alfa AF: 0.0783 Hom.: 971

Bravo AF: 0.0627

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		0.97

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: rs11774231; hg19: chr8-6504316;