Genetic Variant CARMIL1:c.875-494G>A (chr6-25481763-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017640.6(CARMIL1):c.875-494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,138 control chromosomes in the GnomAD database, including 2,156 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 0.15 ( 2156 hom., cov: 32)

Consequence

CARMIL1
NM_017640.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.507

Publications

3 publications found

Variant links:

Genes affected

CARMIL1 (HGNC:21581): (capping protein regulator and myosin 1 linker 1) Involved in several processes, including actin filament network formation; plasma membrane bounded cell projection organization; and positive regulation of cellular component organization. Located in several cellular components, including lamellipodium; macropinosome; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

CARMIL1 links:

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new If you want to explore the variant's impact on the transcript NM_017640.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017640.6. 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
	CARMIL1	NM_017640.6	MANE Select	c.875-494G>A		intron	N/A	NP_060110.4
	CARMIL1	NM_001173977.2		c.875-494G>A		intron	N/A	NP_001167448.1	A0A8V8TRE2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CARMIL1	ENST00000329474.7	TSL:1 MANE Select	c.875-494G>A	intron	N/A	ENSP00000331983.6	Q5VZK9-1
CARMIL1	ENST00000865798.1		c.875-494G>A	intron	N/A	ENSP00000535857.1
CARMIL1	ENST00000911480.1		c.875-494G>A	intron	N/A	ENSP00000581539.1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23224

AN:

152020

Hom.:

2152

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0480

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.169

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.159

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

GnomAD4 genome

AF:

0.153

AC:

23248

AN:

152138

Hom.:

2156

Cov.:

AF XY:

0.155

AC XY:

11506

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0480

AC:

1992

AN:

41522

American (AMR)

AF:

0.198

AC:

3036

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

639

AN:

3468

East Asian (EAS)

AF:

0.172

AC:

892

AN:

5172

South Asian (SAS)

AF:

0.250

AC:

1204

AN:

4814

European-Finnish (FIN)

AF:

0.190

AC:

2004

AN:

10566

Middle Eastern (MID)

AF:

0.164

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.191

AC:

12979

AN:

67984

Other (OTH)

AF:

0.163

AC:

344

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

984

1969

2953

3938

4922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.182

Hom.:

8513

Bravo

AF:

0.150

Asia WGS

AF:

0.211

AC:

731

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.4

(source)

DANN

Benign

0.64

PhyloP100

0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over