7-96491363-G-A

Variant names:

• chr7-96491363-G-A
• rs4727338
• ENST00000611360.4:n.86+4921C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000611360.4(SEM1):​n.86+4921C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: SEM1 ENST00000611360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 28 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEM1	NR_163948.1		n.99+4921C>T		intron	N/A
	SEM1	NR_163949.1		n.99+4921C>T		intron	N/A
	SEM1	NR_163950.1		n.537-4946C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEM1	ENST00000611360.4	TSL:1	n.86+4921C>T		intron	N/A
	SEM1	ENST00000356686.2	TSL:5	c.12+4921C>T		intron	N/A	ENSP00000349114.1
	SEM1	ENST00000615352.4	TSL:5	c.12+4921C>T		intron	N/A	ENSP00000481021.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
DANN	Benign	0.93
PhyloP100		0.42

Splicing

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

Other links and lift over

dbSNP: rs4727338; hg19: chr7-96120675;