rs183860695

chr19-44703663-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001039213.4(CEACAM16):c.352G>A(p.Glu118Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00273 in 1,576,586 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (18 hom.)
• Consequence: CEACAM16 NM_001039213.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.81

Genes affected

CEACAM16 (HGNC:31948): (CEA cell adhesion molecule 16, tectorial membrane component) The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0083652735).
• BP6: Variant 19-44703663-G-A is Benign according to our data. Variant chr19-44703663-G-A is described in ClinVar as [Benign]. Clinvar id is 226506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-44703663-G-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM16	NM_001039213.4	c.352G>A	p.Glu118Lys	missense_variant	3/7	ENST00000587331.7
CEACAM16	XM_017026795.2	c.352G>A	p.Glu118Lys	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM16	ENST00000587331.7	c.352G>A	p.Glu118Lys	missense_variant	3/7	1	NM_001039213.4	P1
CEACAM16-AS1	ENST00000662585.1	n.382-4486C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 336 AN: 152022 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000556

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00329 AC: 676 AN: 205396 Hom.: 3 AF XY: 0.00326 AC XY: 361 AN XY: 110864

Gnomad AFR exome AF: 0.000557

Gnomad AMR exome AF: 0.00244

Gnomad ASJ exome AF: 0.0385

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00232

Gnomad FIN exome AF: 0.0000533

Gnomad NFE exome AF: 0.00244

Gnomad OTH exome AF: 0.00480

GnomAD4 exome AF: 0.00279 AC: 3972 AN: 1424446 Hom.: 18 Cov.: 32 AF XY: 0.00286 AC XY: 2015 AN XY: 703432

Gnomad4 AFR exome AF: 0.000304

Gnomad4 AMR exome AF: 0.00238

Gnomad4 ASJ exome AF: 0.0354

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00233

Gnomad4 FIN exome AF: 0.0000588

Gnomad4 NFE exome AF: 0.00233

Gnomad4 OTH exome AF: 0.00454

GnomAD4 genome AF: 0.00221 AC: 336 AN: 152140 Hom.: 2 Cov.: 32 AF XY: 0.00195 AC XY: 145 AN XY: 74370

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00224

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00354 Hom.: 8

Bravo AF: 0.00296

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000964 AC: 4

ESP6500EA AF: 0.00274 AC: 23

ExAC AF: 0.00244 AC: 294

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 16, 2015	p.Glu118Lys in exon 3 of CEACAM16: This variant is not expected to have clinical significance because it has been identified in 0.5% (188/34916) of European chr omosomes including 1 homozygote by the Exome Aggregation Consortium (ExAC, http: //exac.broadinstitute.org; dbSNP rs183860695). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 17, 2017	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 25, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.25
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.067	T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.0084	T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	0.62	D;D
PrimateAI	Uncertain	0.53	T
Sift4G	Uncertain	0.060	T;T
Vest4		0.61
MVP		0.77
MPC		0.53
ClinPred		0.032	T
GERP RS		5.2
Varity_R		0.22
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.32		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs183860695; hg19: chr19-45206933; COSMIC: COSV69187215;