15-78893535-A-G

Position:

• chr15-78893535-A-G

Variant summary

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

The NM_006791.4(MORF4L1):​c.541-4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,576,866 control chromosomes in the GnomAD database, including 12,328 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1324 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11004 hom.)
• Consequence: MORF4L1 NM_006791.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002623
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

Genes affected

MORF4L1 (HGNC:16989): (mortality factor 4 like 1) Enables protein N-terminus binding activity. Involved in double-strand break repair via homologous recombination and histone modification. Located in nuclear speck. Part of NuA4 histone acetyltransferase complex and Sin3 complex. [provided by Alliance of Genome Resources, Apr 2022]

MORF4L1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORF4L1	NM_006791.4	c.541-4A>G		splice_region_variant, intron_variant		ENST00000426013.7	NP_006782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORF4L1	ENST00000426013.7	c.541-4A>G		splice_region_variant, intron_variant		1	NM_006791.4	ENSP00000408880.2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19594 AN: 152088 Hom.: 1324 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.0982

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.138

GnomAD3 exomes AF: 0.129 AC: 31905 AN: 246378 Hom.: 2272 AF XY: 0.128 AC XY: 17079 AN XY: 133236

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.265

Gnomad SAS exome AF: 0.0933

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.119 AC: 169551 AN: 1424660 Hom.: 11004 Cov.: 27 AF XY: 0.119 AC XY: 84286 AN XY: 710108

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.256

Gnomad4 SAS exome AF: 0.0939

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.129 AC: 19594 AN: 152206 Hom.: 1324 Cov.: 33 AF XY: 0.130 AC XY: 9680 AN XY: 74418

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.0974

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.139

Alfa AF: 0.111 Hom.: 658

Bravo AF: 0.131

Asia WGS AF: 0.145 AC: 505 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.8
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0080
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: rs1836556; hg19: chr15-79185877; COSMIC: COSV58705485; COSMIC: COSV58705485;