Variant rs9972635 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001013838.3(CARMIL2):c.1440-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 1,601,826 control chromosomes in the GnomAD database, including 9,627 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 0.15 ( 3188 hom., cov: 32)

Exomes 𝑓: 0.071 ( 6439 hom. )

Consequence

CARMIL2
NM_001013838.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001198

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.225

Variant links:

Genes affected

CARMIL2 (HGNC:27089): (capping protein regulator and myosin 1 linker 2) This gene encodes a member of the CARMIL (capping protein, Arp2/3, myosin-I linker) family of proteins. The encoded protein interacts with and negatively regulates the heterodimeric capping protein and promotes cell migration. Reduced expression of this gene has been observed in human psoriasis patients. Mutations in this gene cause a human immunodeficiency syndrome characterized by smooth muscle tumors and impaired T-cell function. [provided by RefSeq, May 2017]

CARMIL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-67648677-T-C is Benign according to our data. Variant chr16-67648677-T-C is described in ClinVar as [Benign]. Clinvar id is 1166790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARMIL2	NM_001013838.3 linkuse as main transcript	c.1440-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000334583.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARMIL2	ENST00000334583.11 linkuse as main transcript	c.1440-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001013838.3	A2	Q6F5E8-1

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22529

AN:

152042

Hom.:

3173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0943

Gnomad ASJ

AF:

0.0899

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.0360

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.0552

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.0857

AC:

19627

AN:

229068

Hom.:

1674

AF XY:

0.0873

AC XY:

10866

AN XY:

124510

show subpopulations

Gnomad AFR exome

AF:

0.372

Gnomad AMR exome

AF:

0.0533

Gnomad ASJ exome

AF:

0.0912

Gnomad EAS exome

AF:

0.00234

Gnomad SAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.0368

Gnomad NFE exome

AF:

0.0590

Gnomad OTH exome

AF:

0.0790

GnomAD4 exome

AF:

0.0709

AC:

102829

AN:

1449666

Hom.:

6439

Cov.:

AF XY:

0.0729

AC XY:

52500

AN XY:

720058

show subpopulations

Gnomad4 AFR exome

AF:

0.396

Gnomad4 AMR exome

AF:

0.0565

Gnomad4 ASJ exome

AF:

0.0943

Gnomad4 EAS exome

AF:

0.00138

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.0386

Gnomad4 NFE exome

AF:

0.0570

Gnomad4 OTH exome

AF:

0.0887

GnomAD4 genome

AF:

0.148

AC:

22577

AN:

152160

Hom.:

3188

Cov.:

AF XY:

0.146

AC XY:

10872

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.374

Gnomad4 AMR

AF:

0.0941

Gnomad4 ASJ

AF:

0.0899

Gnomad4 EAS

AF:

0.00329

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.0360

Gnomad4 NFE

AF:

0.0552

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.0709

Hom.:

1116

Bravo

AF:

0.157

Asia WGS

AF:

0.105

AC:

366

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Severe combined immunodeficiency due to CARMIL2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.9

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over