7-95813378-TAAAAA-TAAAAAA

Variant names:

• chr7-95813378-T-TA
• rs35397709
• NM_001135556.2:c.314+56dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001135556.2(DYNC1I1):​c.314+56dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (4708 hom., cov: 0)
  • Exomes 𝑓: 0.28 (906 hom.)
  • Failed GnomAD Quality Control
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.299
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 7-95813378-T-TA is Benign according to our data. Variant chr7-95813378-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1279828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 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.314+56dupA		intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.365+56dupA		intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.365+56dupA		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.314+41_314+42insA		intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.365+41_365+42insA		intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.314+41_314+42insA		intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 36040 AN: 140986 Hom.: 4700 Cov.: 0

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.251

GnomAD2 exomes AF: 0.294 AC: 31554 AN: 107330 AF XY: 0.291

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.273

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.324

Gnomad NFE exome AF: 0.300

Gnomad OTH exome AF: 0.290

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.282 AC: 341468 AN: 1211736 Hom.: 906 Cov.: 20 AF XY: 0.280 AC XY: 168225 AN XY: 600220

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.325 AC: 8572 AN: 26338

American (AMR) AF: 0.237 AC: 5705 AN: 24030

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 5687 AN: 19960

East Asian (EAS) AF: 0.216 AC: 7291 AN: 33810

South Asian (SAS) AF: 0.252 AC: 16587 AN: 65842

European-Finnish (FIN) AF: 0.282 AC: 11252 AN: 39926

Middle Eastern (MID) AF: 0.300 AC: 1381 AN: 4602

European-Non Finnish (NFE) AF: 0.286 AC: 270873 AN: 946990

Other (OTH) AF: 0.281 AC: 14120 AN: 50238

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.256 AC: 36061 AN: 140998 Hom.: 4708 Cov.: 0 AF XY: 0.253 AC XY: 17225 AN XY: 68078

African (AFR) AF: 0.345 AC: 13364 AN: 38764

American (AMR) AF: 0.188 AC: 2659 AN: 14132

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 809 AN: 3312

East Asian (EAS) AF: 0.142 AC: 685 AN: 4824

South Asian (SAS) AF: 0.189 AC: 832 AN: 4402

European-Finnish (FIN) AF: 0.250 AC: 1974 AN: 7892

Middle Eastern (MID) AF: 0.241 AC: 66 AN: 274

European-Non Finnish (NFE) AF: 0.232 AC: 14993 AN: 64576

Other (OTH) AF: 0.252 AC: 490 AN: 1948

Alfa AF: 0.136 Hom.: 196

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35397709;

hg19: chr7-95442690;

Mutation Effect Viewer