1-40067631-C-T

Variant names:

• chr1-40067631-C-T
• rs552626695
• NM_006367.4:c.722C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006367.4(CAP1):​c.722C>T​(p.Pro241Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000756 in 1,573,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: CAP1 NM_006367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.52
• Publications: 0 publications found

Genes affected

CAP1 (HGNC:20040): (cyclase associated actin cytoskeleton regulatory protein 1) The protein encoded by this gene is related to the S. cerevisiae CAP protein, which is involved in the cyclic AMP pathway. The human protein is able to interact with other molecules of the same protein, as well as with CAP2 and actin. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15527835).
• BS2: High AC in GnomAd4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006367.4. 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
	CAP1	NM_006367.4	MANE Select	c.722C>T	p.Pro241Leu	missense	Exon 8 of 13	NP_006358.2	Q01518-1
	CAP1	NM_001105530.2		c.722C>T	p.Pro241Leu	missense	Exon 8 of 13	NP_001099000.2	Q01518-1
	CAP1	NM_001350475.2		c.722C>T	p.Pro241Leu	missense	Exon 9 of 14	NP_001337404.2	Q01518-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAP1	ENST00000372805.8	TSL:1 MANE Select	c.722C>T	p.Pro241Leu	missense	Exon 8 of 13	ENSP00000361891.3	Q01518-1
	CAP1	ENST00000372792.7	TSL:1	c.722C>T	p.Pro241Leu	missense	Exon 8 of 13	ENSP00000361878.2	Q01518-1
	CAP1	ENST00000372797.7	TSL:1	c.722C>T	p.Pro241Leu	missense	Exon 8 of 13	ENSP00000361883.3	Q01518-1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152192 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000134 AC: 31 AN: 231718 AF XY: 0.000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000337

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000206

Gnomad OTH exome AF: 0.000182

GnomAD4 exome AF: 0.0000739 AC: 105 AN: 1421588 Hom.: 0 Cov.: 23 AF XY: 0.0000916 AC XY: 65 AN XY: 709342

African (AFR) AF: 0.0000946 AC: 3 AN: 31724

American (AMR) AF: 0.0000496 AC: 2 AN: 40286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25278

East Asian (EAS) AF: 0.00 AC: 0 AN: 38534

South Asian (SAS) AF: 0.000213 AC: 18 AN: 84660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53212

Middle Eastern (MID) AF: 0.000886 AC: 5 AN: 5642

European-Non Finnish (NFE) AF: 0.0000665 AC: 72 AN: 1083406

Other (OTH) AF: 0.0000850 AC: 5 AN: 58846

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152310 Hom.: 0 Cov.: 31 AF XY: 0.0000940 AC XY: 7 AN XY: 74474

African (AFR) AF: 0.0000963 AC: 4 AN: 41558

American (AMR) AF: 0.000131 AC: 2 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000988 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.000149 AC: 18

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.032
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.5
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.076
Sift	Benign	0.19	T
Sift4G	Benign	0.064	T
Polyphen		0.29	B
Vest4		0.40
MVP		0.73
MPC		0.83
ClinPred		0.35	T
GERP RS		4.9
Varity_R		0.14
gMVP		0.45
Mutation Taster		=37/63	disease causing

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: rs552626695; hg19: chr1-40533303;