chr17-40130817-G-C

Variant names:

• chr17-40130817-G-C
• rs17678694
• NM_001365919.1:c.1376-720G>C

Variant summary

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

The NM_001365919.1(MSL1):​c.1376-720G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 152,320 control chromosomes in the GnomAD database, including 49 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 0.018 (49 hom., cov: 32)
  • Exomes 𝑓: 0.050 (0 hom.)
• Consequence: MSL1 NM_001365919.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 1 publications found

Genes affected

MSL1 (HGNC:27905): (MSL complex subunit 1) Predicted to enable chromatin binding activity. Involved in histone H4-K16 acetylation. Located in nucleoplasm. Part of MSL 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=-0.51).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.0625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365919.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSL1	NM_001365919.1	MANE Select	c.1376-720G>C		intron	N/A	NP_001352848.1
	MSL1	NM_001365920.1		c.1375+1190G>C		intron	N/A	NP_001352849.1
	MSL1	NM_001012241.2		c.587-720G>C		intron	N/A	NP_001012241.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSL1	ENST00000398532.9	TSL:1 MANE Select	c.1376-720G>C		intron	N/A	ENSP00000381543.3
	MSL1	ENST00000579565.5	TSL:1	c.587-720G>C		intron	N/A	ENSP00000462945.1
	MSL1	ENST00000578648.5	TSL:5	c.1375+1190G>C		intron	N/A	ENSP00000462731.1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2774 AN: 152182 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.00886

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.0500 AC: 1 AN: 20 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

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) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0625 AC: 1 AN: 16

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0182 AC: 2774 AN: 152300 Hom.: 49 Cov.: 32 AF XY: 0.0173 AC XY: 1287 AN XY: 74478

African (AFR) AF: 0.00522 AC: 217 AN: 41550

American (AMR) AF: 0.0123 AC: 188 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00787 AC: 38 AN: 4826

European-Finnish (FIN) AF: 0.00886 AC: 94 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0307 AC: 2085 AN: 68026

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.0154 Hom.: 7

Bravo AF: 0.0185

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		2.8
Mutation Taster		=100/0	polymorphism

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: rs17678694; hg19: chr17-38287070;