7-95804844-C-T

Variant names:

• chr7-95804844-C-T
• rs41278809
• NM_001135556.2:c.108+7C>T

Variant summary

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

The NM_001135556.2(DYNC1I1):​c.108+7C>T variant causes a splice region, 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DYNC1I1 NM_001135556.2 splice_region, intron
• Scores: Splicing: ADA: 0.0001424
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 4 publications found

Genes affected

DYNC1I1 (HGNC:2963): (dynein cytoplasmic 1 intermediate chain 1) Enables spectrin binding activity. Involved in vesicle transport along microtubule. Located in several cellular components, including kinetochore; recycling endosome; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135556.2. 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
	DYNC1I1	NM_001135556.2	MANE Select	c.108+7C>T		splice_region intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.108+7C>T		splice_region intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.108+7C>T		splice_region intron	N/A	NP_001265350.1	O14576-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1I1	ENST00000447467.6	TSL:1 MANE Select	c.108+7C>T		splice_region intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.108+7C>T		splice_region intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.108+7C>T		splice_region intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.25
DANN	Benign	0.55
PhyloP100		-2.5

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0060
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: rs41278809; hg19: chr7-95434156; COSMIC: COSV100269147;