7-899208-C-T

Variant names:

• chr7-899208-C-T
• rs61995731
• NM_006869.4:c.921G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_006869.4(ADAP1):​c.921G>A​(p.Thr307Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00504 in 1,612,652 control chromosomes in the GnomAD database, including 343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (174 hom., cov: 34)
  • Exomes 𝑓: 0.0028 (169 hom.)
• Consequence: ADAP1 NM_006869.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0790
• Publications: 1 publications found

Genes affected

ADAP1 (HGNC:16486): (ArfGAP with dual PH domains 1) Enables GTPase activator activity. Involved in regulation of GTPase activity. Located in cytosol; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

COX19 (HGNC:28074): (cytochrome c oxidase assembly factor COX19) COX19 encodes a cytochrome c oxidase (COX)-assembly protein. The S. cerevisiae Cox19 protein may play a role in metal transport to the mitochondrial intermembrane space and assembly of complex IV of the mitochondrial respiratory chain (Sacconi et al., 2005 [PubMed 16212937]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.055).
• BP6: Variant 7-899208-C-T is Benign according to our data. Variant chr7-899208-C-T is described in ClinVar as Benign. ClinVar VariationId is 776189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.079 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006869.4. 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
	ADAP1	NM_006869.4	MANE Select	c.921G>A	p.Thr307Thr	synonymous	Exon 10 of 11	NP_006860.2	O75689-1
	ADAP1	NM_001284308.2		c.954G>A	p.Thr318Thr	synonymous	Exon 10 of 11	NP_001271237.2	O75689-2
	ADAP1	NM_001284309.2		c.705G>A	p.Thr235Thr	synonymous	Exon 10 of 11	NP_001271238.2	O75689-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAP1	ENST00000265846.10	TSL:1 MANE Select	c.921G>A	p.Thr307Thr	synonymous	Exon 10 of 11	ENSP00000265846.5	O75689-1
	ADAP1	ENST00000539900.5	TSL:2	c.954G>A	p.Thr318Thr	synonymous	Exon 10 of 11	ENSP00000442682.1	O75689-2
	ADAP1	ENST00000943017.1		c.939G>A	p.Thr313Thr	synonymous	Exon 10 of 11	ENSP00000613076.1

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4026 AN: 152204 Hom.: 175 Cov.: 34

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0220

GnomAD2 exomes AF: 0.00679 AC: 1672 AN: 246152 AF XY: 0.00475

Gnomad AFR exome AF: 0.0950

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000453

Gnomad OTH exome AF: 0.00298

GnomAD4 exome AF: 0.00281 AC: 4097 AN: 1460330 Hom.: 169 Cov.: 32 AF XY: 0.00242 AC XY: 1760 AN XY: 726502

African (AFR) AF: 0.0944 AC: 3160 AN: 33474

American (AMR) AF: 0.00440 AC: 197 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51980

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.000307 AC: 341 AN: 1111940

Other (OTH) AF: 0.00588 AC: 355 AN: 60368

GnomAD4 genome AF: 0.0264 AC: 4024 AN: 152322 Hom.: 174 Cov.: 34 AF XY: 0.0256 AC XY: 1910 AN XY: 74490

African (AFR) AF: 0.0914 AC: 3798 AN: 41560

American (AMR) AF: 0.00928 AC: 142 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68024

Other (OTH) AF: 0.0218 AC: 46 AN: 2110

Alfa AF: 0.00717 Hom.: 29

Bravo AF: 0.0304

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000533

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
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.8
DANN	Benign	0.90
PhyloP100		-0.079
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs61995731; hg19: chr7-938845; COSMIC: COSV56210414; COSMIC: COSV56210414;