15-78893535-A-G

Variant names:

• chr15-78893535-A-G
• rs1836556
• NM_006791.4:c.541-4A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MORF4L1	NM_006791.4	c.541-4A>G		splice_region_variant, intron_variant	Intron 8 of 11	ENST00000426013.7	NP_006782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORF4L1	ENST00000426013.7	c.541-4A>G		splice_region_variant, intron_variant	Intron 8 of 11	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

GnomAD2 exomes AF: 0.129 AC: 31905 AN: 246378 AF XY: 0.128

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.112 AC: 3642 AN: 32608

American (AMR) AF: 0.111 AC: 4846 AN: 43824

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2943 AN: 25742

East Asian (EAS) AF: 0.256 AC: 9995 AN: 39056

South Asian (SAS) AF: 0.0939 AC: 7929 AN: 84406

European-Finnish (FIN) AF: 0.140 AC: 7437 AN: 53172

Middle Eastern (MID) AF: 0.102 AC: 578 AN: 5648

European-Non Finnish (NFE) AF: 0.116 AC: 125004 AN: 1081152

Other (OTH) AF: 0.122 AC: 7177 AN: 59052

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.119 AC: 4930 AN: 41534

American (AMR) AF: 0.134 AC: 2045 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3470

East Asian (EAS) AF: 0.262 AC: 1358 AN: 5174

South Asian (SAS) AF: 0.0974 AC: 471 AN: 4834

European-Finnish (FIN) AF: 0.137 AC: 1452 AN: 10586

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8438 AN: 68002

Other (OTH) AF: 0.139 AC: 294 AN: 2116

Alfa AF: 0.115 Hom.: 894

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
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1836556; hg19: chr15-79185877; COSMIC: COSV58705485; COSMIC: COSV58705485;