rs73597578

Variant names:

• chr16-67645445-C-T
• rs73597578
• NM_001013838.3:c.41-95C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001013838.3(CARMIL2):​c.41-95C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,384,752 control chromosomes in the GnomAD database, including 10,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2390 hom., cov: 33)
  • Exomes 𝑓: 0.11 (8068 hom.)
• Consequence: CARMIL2 NM_001013838.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.95
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• severe combined immunodeficiency due to CARMIL2 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-67645445-C-T is Benign according to our data. Variant chr16-67645445-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013838.3. 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
	CARMIL2	NM_001013838.3	MANE Select	c.41-95C>T		intron	N/A	NP_001013860.1	Q6F5E8-1
	CARMIL2	NM_001438835.1		c.41-95C>T		intron	N/A	NP_001425764.1
	CARMIL2	NM_001438244.1		c.41-95C>T		intron	N/A	NP_001425173.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL2	ENST00000334583.11	TSL:1 MANE Select	c.41-95C>T		intron	N/A	ENSP00000334958.5	Q6F5E8-1
	CARMIL2	ENST00000545661.5	TSL:1	c.41-95C>T		intron	N/A	ENSP00000441481.1	Q6F5E8-2
	CARMIL2	ENST00000696175.1		c.41-95C>T		intron	N/A	ENSP00000512465.1	A0A8Q3SII9

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24099 AN: 152150 Hom.: 2384 Cov.: 33

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.107 AC: 131302 AN: 1232484 Hom.: 8068 Cov.: 18 AF XY: 0.107 AC XY: 65672 AN XY: 614758

African (AFR) AF: 0.273 AC: 7693 AN: 28176

American (AMR) AF: 0.152 AC: 5375 AN: 35290

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 2083 AN: 23972

East Asian (EAS) AF: 0.0339 AC: 1185 AN: 34968

South Asian (SAS) AF: 0.124 AC: 9452 AN: 76162

European-Finnish (FIN) AF: 0.149 AC: 7095 AN: 47766

Middle Eastern (MID) AF: 0.0925 AC: 463 AN: 5004

European-Non Finnish (NFE) AF: 0.0992 AC: 92194 AN: 928910

Other (OTH) AF: 0.110 AC: 5762 AN: 52236

GnomAD4 genome AF: 0.159 AC: 24141 AN: 152268 Hom.: 2390 Cov.: 33 AF XY: 0.159 AC XY: 11868 AN XY: 74466

African (AFR) AF: 0.277 AC: 11522 AN: 41528

American (AMR) AF: 0.144 AC: 2209 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 325 AN: 3470

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5190

South Asian (SAS) AF: 0.121 AC: 584 AN: 4830

European-Finnish (FIN) AF: 0.158 AC: 1682 AN: 10620

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7289 AN: 68012

Other (OTH) AF: 0.141 AC: 298 AN: 2112

Alfa AF: 0.142 Hom.: 235

Bravo AF: 0.162

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.19
DANN	Benign	0.53
PhyloP100		-1.9
PromoterAI		0.030	Neutral
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

Other links and lift over

dbSNP: rs73597578; hg19: chr16-67679348; COSMIC: COSV58025650; COSMIC: COSV58025650;