chr7-96490169-G-A

Variant names:

• chr7-96490169-G-A
• rs10429035
• ENST00000611360.4:n.87-3752C>T

Variant summary

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

The ENST00000611360.4(SEM1):​n.87-3752C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,920 control chromosomes in the GnomAD database, including 13,277 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 0.38 (13277 hom., cov: 32)
• Consequence: SEM1 ENST00000611360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561
• Publications: 17 publications found

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]

LOC105375411 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000611360.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEM1	NR_163948.1		n.100-3752C>T		intron	N/A
	SEM1	NR_163949.1		n.100-3752C>T		intron	N/A
	SEM1	NR_163950.1		n.537-3752C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEM1	ENST00000611360.4	TSL:1	n.87-3752C>T		intron	N/A
	SEM1	ENST00000356686.2	TSL:5	c.13-3752C>T		intron	N/A	ENSP00000349114.1	Q6ZVN7-1
	SEM1	ENST00000615352.4	TSL:5	c.13-3752C>T		intron	N/A	ENSP00000481021.1	B7ZVW6

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57543 AN: 151802 Hom.: 13231 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.379 AC: 57644 AN: 151920 Hom.: 13277 Cov.: 32 AF XY: 0.379 AC XY: 28110 AN XY: 74258

African (AFR) AF: 0.659 AC: 27330 AN: 41486

American (AMR) AF: 0.296 AC: 4519 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1212 AN: 3464

East Asian (EAS) AF: 0.184 AC: 948 AN: 5140

South Asian (SAS) AF: 0.300 AC: 1443 AN: 4802

European-Finnish (FIN) AF: 0.270 AC: 2846 AN: 10530

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18105 AN: 67936

Other (OTH) AF: 0.370 AC: 780 AN: 2108

Alfa AF: 0.302 Hom.: 29682

Bravo AF: 0.389

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.77
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10429035; hg19: chr7-96119481;