rs9320231

Positions:

• chr6-107749035-A-G

Variant summary

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

The NM_198081.5(SCML4):​c.286+649T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,036 control chromosomes in the GnomAD database, including 6,408 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 0.27 (6408 hom., cov: 32)
• Consequence: SCML4 NM_198081.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

Genes affected

SCML4 (HGNC:21397): (Scm polycomb group protein like 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCML4	NM_198081.5	c.286+649T>C		intron_variant		ENST00000369020.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCML4	ENST00000369020.8	c.286+649T>C		intron_variant		5	NM_198081.5	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40306 AN: 151918 Hom.: 6388 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.265 AC: 40362 AN: 152036 Hom.: 6408 Cov.: 32 AF XY: 0.262 AC XY: 19489 AN XY: 74330

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.235

Alfa AF: 0.227 Hom.: 780

Bravo AF: 0.273

Asia WGS AF: 0.255 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.46

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: rs9320231; hg19: chr6-108070239;