rs17617068

Positions:

• chr5-179741096-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014757.5(MAML1):​c.315+7669T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,092 control chromosomes in the GnomAD database, including 4,588 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 0.23 (4588 hom., cov: 31)
• Consequence: MAML1 NM_014757.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

Genes affected

MAML1 (HGNC:13632): (mastermind like transcriptional coactivator 1) This protein is the human homolog of mastermind, a Drosophila protein that plays a role in the Notch signaling pathway involved in cell-fate determination. There is in vitro evidence that the human homolog forms a complex with the intracellular portion of human Notch receptors and can increase expression of a Notch-induced gene. This evidence supports its proposed function as a transcriptional co-activator in the Notch signaling pathway. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAML1	NM_014757.5	c.315+7669T>C		intron_variant		ENST00000292599.4	NP_055572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAML1	ENST00000292599.4	c.315+7669T>C		intron_variant		1	NM_014757.5	ENSP00000292599.3

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34968 AN: 151974 Hom.: 4588 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.230 AC: 34980 AN: 152092 Hom.: 4588 Cov.: 31 AF XY: 0.229 AC XY: 17044 AN XY: 74352

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.236

Alfa AF: 0.275 Hom.: 5815

Bravo AF: 0.213

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs17617068; hg19: chr5-179168097;