7-95804844-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001135556.2(DYNC1I1):​c.108+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 1,550,238 control chromosomes in the GnomAD database, including 7,489 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (608 hom., cov: 32)
  • Exomes 𝑓: 0.097 (6881 hom.)
• Consequence: DYNC1I1 NM_001135556.2 splice_region, intron
• Scores: Splicing: ADA: 0.0001070
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-95804844-C-G is Benign according to our data. Variant chr7-95804844-C-G is described in ClinVar as Benign. ClinVar VariationId is 402810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

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>G		splice_region intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.108+7C>G		splice_region intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.108+7C>G		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>G		splice_region intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.108+7C>G		splice_region intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.108+7C>G		splice_region intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12341 AN: 151888 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0833

GnomAD2 exomes AF: 0.0846 AC: 13485 AN: 159360 AF XY: 0.0854

Gnomad AFR exome AF: 0.0382

Gnomad AMR exome AF: 0.0707

Gnomad ASJ exome AF: 0.0851

Gnomad EAS exome AF: 0.0296

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0979

Gnomad OTH exome AF: 0.0999

GnomAD4 exome AF: 0.0965 AC: 134933 AN: 1398232 Hom.: 6881 Cov.: 31 AF XY: 0.0959 AC XY: 66208 AN XY: 690064

African (AFR) AF: 0.0402 AC: 1263 AN: 31438

American (AMR) AF: 0.0715 AC: 2566 AN: 35872

Ashkenazi Jewish (ASJ) AF: 0.0864 AC: 2176 AN: 25184

East Asian (EAS) AF: 0.0385 AC: 1381 AN: 35890

South Asian (SAS) AF: 0.0777 AC: 6143 AN: 79064

European-Finnish (FIN) AF: 0.129 AC: 6354 AN: 49294

Middle Eastern (MID) AF: 0.0995 AC: 565 AN: 5676

European-Non Finnish (NFE) AF: 0.101 AC: 109248 AN: 1077852

Other (OTH) AF: 0.0904 AC: 5237 AN: 57962

GnomAD4 genome AF: 0.0813 AC: 12351 AN: 152006 Hom.: 608 Cov.: 32 AF XY: 0.0821 AC XY: 6097 AN XY: 74296

African (AFR) AF: 0.0400 AC: 1658 AN: 41464

American (AMR) AF: 0.0821 AC: 1253 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3470

East Asian (EAS) AF: 0.0304 AC: 157 AN: 5162

South Asian (SAS) AF: 0.0727 AC: 350 AN: 4816

European-Finnish (FIN) AF: 0.138 AC: 1462 AN: 10566

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0994 AC: 6753 AN: 67944

Other (OTH) AF: 0.0825 AC: 174 AN: 2110

Alfa AF: 0.0728 Hom.: 165

Bravo AF: 0.0768

Asia WGS AF: 0.0510 AC: 177 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	DYNC1I1-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.20
DANN	Benign	0.52
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
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;