7-96504219-T-C

Position:

• chr7-96504219-T-C

Variant summary

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

The ENST00000618105.4(SEM1):​n.*116+2404A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 151,952 control chromosomes in the GnomAD database, including 39,768 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 0.72 (39768 hom., cov: 31)
• Consequence: SEM1 ENST00000618105.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808

Genes affected

SEM1 (HGNC:10845): (SEM1 26S proteasome subunit) The product of this gene has been localized within the split hand/split foot malformation locus SHFM1 at chromosome 7. It has been proposed to be a candidate gene for the autosomal dominant form of the heterogeneous limb developmental disorder split hand/split foot malformation type 1. In addition, it has been shown to directly interact with BRCA2. It also may play a role in the completion of the cell cycle. [provided by RefSeq, Jul 2008]

SEM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEM1	NR_163950.1	n.536+2404A>G		intron_variant
SEM1	NR_163951.1	n.329+2404A>G		intron_variant
SEM1	NR_163952.1	n.458+2404A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEM1	ENST00000466986.5	n.*60+2404A>G		intron_variant		2		ENSP00000481400.1
SEM1	ENST00000613919.4	n.*252+2404A>G		intron_variant		2		ENSP00000482085.1
SEM1	ENST00000617133.4	n.*198+2404A>G		intron_variant		2		ENSP00000484726.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109132 AN: 151830 Hom.: 39703 Cov.: 31

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.678

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

GnomAD4 genome AF: 0.719 AC: 109264 AN: 151952 Hom.: 39768 Cov.: 31 AF XY: 0.722 AC XY: 53652 AN XY: 74262

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.679

Alfa AF: 0.674 Hom.: 41620

Bravo AF: 0.723

Asia WGS AF: 0.790 AC: 2746 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7781370; hg19: chr7-96133531;